OBJECTIVE:The Mediterranean Diet (MedDiet) and physical activity (PA) can enhance mood and support psychological wellbeing in adults. However, the combined effect is relatively unknown. MedWalk aimed to determine the combined effect on wellbeing, psychological health and quality of life (QoL), compared to a control group. DESIGN:This is an analysis of secondary outcomes from the MedWalk 12-month cluster-randomised controlled trial. Participants completed the Total and Secure Flourishing Index (FI), the four domain General Health Questionnaire (GHQ-28) and the 8-domain Assessment of Quality of Life (AQoL-8D). Data were analysed using general linear models using change scores (FI and AQoL-8D) or generalised linear mixed models with a time × group interaction effect (GHQ-28). SETTING:Independent living facilities across South Australia and Victoria in 2021-2022. PARTICIPANTS:One hundred and sixty-one older men and women. RESULTS:Participants were 74·9 ± 5·9 years of age and predominantly female (74 %). A greater improvement was found for the MedWalk group (marginal means (MM) = 1·65, se = 1·36) than the control group (MM = -2·50, se = 1·32) for the Total Flourish score (P = 0·003) and Secure Flourish score (P = 0·009) ((MM = 1·06, se = 1·65) v. (MM = -3·34, se = 1·61)) from baseline to 6 months. The MedWalk group (MM = 0·021, se = 0·014) had more positive changes (P = 0·048) to the Mental Health AQoL-8D domain than the control group (MM = -0·007, se = 0·014). No significant group × time interactions were identified for the GHQ-28. CONCLUSIONS:Combined MedDiet and walking interventions can modify psychological health, wellbeing and QoL in relatively healthy populations.

Already in its third edition, the Goals in Nutrition Science platform covers a five-year timeframe per volume, thus spanning 15 years from 2015 to 2030 (1, 2). This period aligns with the Sustainable Development Goals, and, in practice, these 5-year updates do capture major shifts in the field. As the second quarter of the 21st century unfolds, it increasingly appears that much of the widely promoted food technology has not delivered or is not yet ready. Nutrition, food security, and sustainability are therefore best treated as inseparable challenges within complex, adaptive food systems, where progress depends on addressing biology, behavior, markets, policy, and environmental constraints together rather than through isolated, linear interventions. Nutrition science matters because it sits at the hinge between human biology and the real-world conditions that determine what people can access, afford, choose, and safely consume. As food systems become more interconnected and more exposed to climate, conflict, and market volatility, the field is shifting from mainly reductionist problem solving toward approaches that can handle feedback, tradeoffs, and equity in context. Pursuing the goals set out here is not only a scientific agenda, but a planetary health imperative: sustainable food systems must secure current and future nutrition while balancing environmental stewardship, health, and socio-economic stability across the pathway from production to consumption and waste. Overall, the agenda points toward a new chapter of nutrition science that integrates the right level of complexity by combining deep disciplinary insight with better integrated systems approaches, and by mobilizing coordinated action.Johannes le Coutre, Field Chief Editor, Frontiers in Nutrition.

Background: Behaviour-change outcomes are often incompletely reported in multidomain trials. We evaluated behaviour change during a 12-month Mediterranean diet (MedDiet) and physical activity (PA) intervention.Participants and Setting: Adults aged 60 to 90 years without cognitive impairment, independently living in two Australian cities.Methods: n=83 participants (MedWalk group) were supported over 12 months to consume a MedDiet and engage in at least 150 minutes of moderate to vigorous PA (MVPA) per week. Control group participants (n=73) maintained habitual diet and PA. Four validated measures (MedWalk MedDiet Adherence Screener (MW-MEDAS), MedDiet Score, accelerometry-derived MVPA and MET minutes by International Physical Activity Questionnaire-elderly) were analysed separately and combined into a total adherence score to determine change in behaviour from baseline. Differences within and between groups were analysed at baseline, 6-months and 12-months using linear mixed effect modelling, controlling for predictors of attrition and baseline group differences.Results: Participants were 74% female, with a mean±SD age of 74.9 ± 5.9 years. After 12 months, MW-MEDAS had increased by an average of 3.3/14 points, and total adherence score by 1.4/8 points in the MedWalk group (p<.001), with no significant change in the control group. There were no significant changes in dietary behaviours in the control group, and MVPA declined in both groups at 6 months.Conclusions: The MedWalk intervention improved overall adherence among older adults over 12 months, driven by an increase in MedDiet adherence. PA did not increase, potentially due to high baseline PA or challenges in changing PA behaviours.

Ginseng has a longstanding reputation as an adaptogen, antistress agent and cognitive enhancer. We conducted a systematic review of randomised controlled studies into the cognitive effects of ginseng in non-clinical populations. The initial search captured 1802 records, of which fourteen articles fulfilled the inclusion criteria and were included in this review. The majority of the studies (N = 11) examined the effects of standardized extracts of Panax ginseng (Asian ginseng), with most (N = 8) using a standardised extract. The other three used a standardised extract of Panax quinquefolius (American ginseng). All but one study included acute assessment ranging from 1 h to 6 h post-administration. Four studies included a ‘chronic’ assessment ranging from 8 days to 12 weeks, three of which included ‘acute-on-chronic’ evaluations. Overall, the effects of P. ginseng tended to benefit accuracy of secondary memory (although there was evidence of a speed accuracy trade-off for specific doses), and to some degree attentional processes. P. quinquefolius had a more positive impact on attentional measures and working memory/executive functions. These effects are likely due to differences in ginsenoside profiles and other components via action on numerous systems, including neurotransmitter systems and glucocorticoid and estrogen receptors. Although there were some methodological consistencies across studies, different cognitive measures and extracts were utilised. Notably, the studies which did not specify the ginsenoside constituents of the extract used did not report cognitive benefits, emphasising the need for standardisation and characterisation.

BACKGROUND:Recent meta-analyses of randomized controlled trials have raised concerns that treatment with omega-3 fatty acids may increase the risk of atrial fibrillation (AF). However, these meta-analyses included at most 8 trials. The aim of this current meta-analysis was to expand the search by including other eligible omega-3 randomized controlled trials with AF incidence data, incorporating both published and unpublished data. METHODS:Eligible studies were randomized controlled trials investigating daily doses of ≥500 mg/d of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Additional inclusion criteria included ≥12 months of treatment with EPA/DHA, participants ≥50 years of age, and, where possible, the absence of known AF/atrial flutter at baseline. The primary outcome was the occurrence of new-onset AF. Our primary hypothesis was that risk for AF would simultaneously depend on both omega-3 dose (above or below 1500 mg/d) and background cardiovascular disease risk status, and that their combined impact on AF risk would be synergistic. RESULTS:A total of 35 randomized controlled trials (37 data sets; n=114 592) were included in this meta-analysis. Only studies including patients at high-risk for cardiovascular disease who were treated with high-doses of EPA/DHA (>1500 mg/d) showed a statistically significant increase in AF risk with a pooled odds ratio (OR) of 1.43 (95% CI, 1.14-1.79) and an absolute risk difference of 0.8% (0.40%-1.1%). None of the other 3 groups showed statistically significant levels of AF risk (odds ratios, 1.07 [high risk-low dose], 1.06 [low risk-low dose], and 1.03 [low risk-high dose]). CONCLUSIONS:This meta-analysis suggests that high-dose EPA/DHA treatment is associated with an increased risk of AF in patients at high cardiovascular disease risk, whereas low-dose EPA/DHA does not appear to increase AF risk, even in high-risk populations. Further prospective studies are needed to evaluate any potential increased risk of higher doses balanced against potential benefits.

A 2019 study revealed more than 80 products available online with implied benefits to alcohol hangover. Since then, several developments may have influenced the market. In order to gauge the extent to which this may have changed in the ensuing 5 years, two market evaluations (25 March 2023 and 7 November 2024) were conducted via the online web shop www.amazon.com , using the search term “hangover treatment.” In 2023, there were 38 different hangover products available. The most common dosage forms were capsules (14) and tablets (6), and most frequently reported ingredients were dihydromyricetin (DHM, 52.6% of products), vitamin B1 (42.1%), vitamin B12 (42.1%), sodium (42.1%), and vitamin B6 (39.5%). Only one product contained N-acetyl L-cysteine. Exactly half of the marketed products (19, 50.0%) made illegal disease modification claims. The second market evaluation (7 November 2024) revealed 46 hangover products. The most common dosage forms were capsules (18) and transdermal patches (13), and the most frequently reported ingredients were vitamin B6 (56.5% of products), vitamin C (54.3%), vitamin B1 (50.0%), and vitamin B12 (50.0%). Also, DHM (47.8%) and milk thistle extract (47.8%) were popular. In conclusion, over the 5 years to 2024 the US hangover product market has dramatically changed, including a significant reduction in the number of marketed hangover products. DHM, vitamins, and minerals remained the most popular ingredients of hangover products. Illegal disease claims were made by 41.3% of the marketed products. Of concern, the efficacy to prevent or reduce alcohol hangover has not been demonstrated for any product on the US hangover market.

In some research, it is important to conduct cognitive assessments in an everyday setting. Both tablet PCs and mobile phones have been used in this context. The purpose of this study was to examine whether a mobile test battery yields similar results on a mobile phone (screen size 6 cm diagonal) and a tablet (18 cm). Thirty-nine healthy volunteers (aged 18–30) completed five training sessions and one final “test” session per device. The 18-minute test battery consisted of six tests, measuring attention (Number Pairs Test, NP and Arrow Flankers Test, AF), psychomotor functioning (Arrow reaction time test, AR), working memory (Memory scanning test, MS), paired associate learning (Shape pairs, SP), and comprehension (Serial sevens, SS). Outcome measures were mean reaction time (RT) and the percentage of errors. RT scores over the practice runs indicated that AR and AF required only a single familiarization run, while other tests needed 3–4 runs to achieve stable performance. No difference was seen in practice effects between the platforms. Test scores were similar for the platforms with minimal differences between phone and tablet scores (effect sizes < 0.25). Correlations between phone and tablet scores were in the range 0.53–0.82, except one measure, SP errors, where the correlation was much lower. Taken together, these results indicate that there is generally good agreement between data obtained from phones and tablets with very different screen sizes. Phones with small screens are suitable for assessing cognition in an everyday setting. Training on the tests is recommended to achieve stable performance before the start of experimental sessions.

Background: Fear of COVID-19 has been associated with adverse mental and physical health outcomes, yet evidence from the Netherlands is limited. This study investigated associations between fear of COVID-19, mood, quality of life, immune fitness, and related health variables during the first Dutch national lockdown and identified key predictors of fear. Methods: In June–July 2020, n = 1020 Dutch adults completed an online survey assessing demographics, personality, mental resilience, pain sensitivity, pain catastrophizing, alcohol use, immune fitness, and mood. Retrospective ratings were provided for the pre-pandemic period (January–March 2020) and the first lockdown (March–May 2020). Fear of COVID-19 was measured using a modified Fear of COVID-19 Scale. Results: Overall, 13.2% of participants reported significant fear of COVID-19, which was associated with poorer mood, reduced quality of life, lower immune fitness, more severe COVID-19 symptoms, greater pain sensitivity, and higher levels of pain catastrophizing. Regression analysis explained 19.6% of the variance, with pre-pandemic anxiety (8.7%) and poorer immune fitness (3.4%) as the strongest predictors of fear of COVID-19, followed by lower psychoticism, lower mental resilience, older age, greater helplessness, and greater extraversion. Discussion: These findings suggest that a minority experienced high levels of fear of COVID-19 with substantial consequences, including negative effects on mood, immune fitness, and quality of life. The strong association with pre-existing anxiety and immune fitness highlights the need for early identification and targeted interventions for vulnerable groups to reduce psychological and physical health impacts in future public health crises.

APOE4, a key risk factor for Alzheimer's disease, influences gut microbiota and microbial metabolites (e.g. amino acids and dietary fiber (DF) derived short-chain fatty acids (SCFAs)). However, its role in modulating microbiota-driven DF metabolism and its effect on cognitive status remains unclear. This cross-sectional study (n = 170) investigates the association between APOE4 genotype, DF consumption, and metabolism in individuals with subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) compared to healthy controls (HC). Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and 1H NMR metabolomic techniques were used to quantify SCFAs in serum and fecal samples, respectively. Gut microbiota speciation was carried out by 16S rRNA amplicon sequencing. We found that DF intake was significantly associated with APOE4 genotype and cognitive status, with lower consumption in APOE4 carriers (p < 0.05) and those with cognitive impairment (SCI and MCI) (p = 0.03). Differences (p < 0.05) in gut microbiota (both α- and β-diversity) and SCFAs were evident between APOE4 and non-APOE4 carriers, with stronger associations with DF consumption and cognitive status evident in non-APOE4 carriers. These findings suggest that targeting DF-induced changes in gut microbiota and serum SCFAs may be an effective strategy for mitigating cognitive impairment, but primarily in non-APOE4 carriers.

Situational factors can influence cognitive performance and should be considered for conducting cognitive assessments. The objective of this project was to develop a checklist for Cognitive Assessment Requirements (CARE) to identify these situational factors before conducting cognitive assessments and account for them. This study employed a four-round Delphi approach involving 22 experts to identify situational factors that can impact cognitive assessment results. The development of a robust and well-balanced checklist was guided by a consensus-driven approach, which considered metrics such as Interquartile Deviation (IQD) (> 1.00), Percentage of Positive Responses (PPR, above 60%), and mean importance ratings (< 3 on a 5-point Likert scale) to assess both degree of agreement and item importance. Consensus was reached, leading to a 14-item checklist to evaluate cognitive assessment requirements. These items were categorized into six groups: Acute Illness or Physical Discomfort, Medication Effects and Substance Use, Sleep Quality and Fatigue, Emotional State, Language factors, and Environmental factors. The CARE can be employed prior to cognitive assessments to identify situational factors of relevance to the individual client, thereby creating a more favorable environment for cognitive evaluation, and enhancing the reliability of the assessment findings. Furthermore, the CARE can help determine the level of confidence in the results by assessing whether the conditions are conducive to testing or if situational factors may undermine the validity of the evaluation.

INTRODUCTION:The use of products to prevent or reduce alcohol hangovers is increasingly popular. The aim of this study was to evaluate and compare the alcohol hangover product markets of the United Kingdom, Australia and Japan. METHODS:The website www.Amazon.com was searched, using the terms 'hangover treatment' and 'hangover cure', to identify hangover products sold in the United Kingdom, Australia and Japan. Dosage forms, ingredients and their amounts per serving were recorded and compared between the three countries. RESULTS:The market evaluations for the United Kingdom and Australia each revealed N = 19 hangover products, and 24 hangover products were found for Japan. The products from the three markets were quite distinct, with none of the hangover products being marketed in all three countries. The most popular ingredients in United Kingdom were potassium (63.2%), sodium (57.9%) and vitamin C (52.6%). The most common ingredients in Australia were vitamin B1, vitamin B6, vitamin B12 and sodium (all 47.4%). In Japan, curcumin (45.8%), L-ornithine (29.2%), vitamin C (20.8%) and vitamin B2 (20.8%) were the most popular ingredients. Most popular dosage forms also differed between the countries, with powders being most popular in the United Kingdom (42.1%), tablets in Japan (50.0%), and capsules (31.6%) and drinks (26.3%) in Australia. DISCUSSION AND CONCLUSIONS:Both ingredients and dosage forms of hangover products differed between the United Kingdom, Australia and Japan. Products also differed from the United States, illustrating the importance of cross-cultural comparisons. As these are currently lacking, double-blind, placebo-controlled clinical trials are needed to demonstrate the efficacy and safety of marketed hangover products.

Abstract The rising incidence of neurodegenerative diseases in an ageing global population has shifted research focus toward modifiable risk factors, such as diet. Despite potential links between dietary patterns and brain health, inconsistencies in neuroimaging outcomes underscore a gap in understanding how diet impacts brain ageing. This study explores the relationship between three dietary patterns—Mediterranean (MeDi), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND)—and cognitive outcomes as well as brain connectivity. The study aimed to assess the association of these diets with brain structure and cognitive function, involving a middle-aged healthy group and an older cohort with subjective cognitive decline (SCD). The study included cognitive assessments and diffusion-weighted MRI data to analyse white matter microstructural integrity. Participants comprised 55 older individuals with SCD (54.5% female, mean age = 64) and 52 healthy middle-aged individuals (48.1% female, mean age = 53). Age inversely correlated with certain cognitive functions and global brain metrics, across both cohorts. Adherence to the MeDi, DASH, and MIND diets showed no significant cognitive or global brain metric improvements after adjusting for covariates (age, education, BMI). Network-based statistics (NBS) analysis revealed differences in brain subnetworks based on DASH diet adherence levels in the SCD cohort. In the healthy cohort, lower white matter connectivity was associated with reduced adherence to MIND and DASH diets. Ultimately, the study found no strong evidence connecting dietary patterns to cognitive or brain connectivity outcomes. Future research should focus on longitudinal studies and refine dietary assessments.

Background Recent meta-analyses of randomized controlled trials (RCTs) have raised concerns that treatment with omega-3 fatty acids may increase risk of atrial fibrillation (AF). However, these meta-analyses included at most eight trials. The aim of this current meta-analysis was to expand the search by including other eligible omega-3 RCTs with AF incidence data, incorporating both published and unpublished data. Methods Eligible studies were RCTs investigating daily doses of ≥500 mg/d of docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). Additional inclusion criteria included ≥12 months treatment with EPA/DHA, participants ≥ 50 years of age, and where possible, the absence of known AF/atrial flutter at baseline. The primary outcome was occurrence of new-onset AF. Our primary hypothesis was that risk for AF would simultaneously depend on both omega-3 dose (above or below 1500 mg/d) and background cardiovascular disease (CVD) risk status, and that their combined impact on AF risk would be synergistic. Results A total of 34 RCTs (36 datasets; n=114,326) were included in this meta-analysis. Only studies including patients at high-risk for CVD who were treated with high-doses of EPA/DHA (>1500 mg/day) showed a statistically significant increase in AF risk with a pooled odds ratio (OR) of 1.48 (95% CI, 1.21-1.81) and an absolute risk difference of 0.8% (0.40-1.1%). None of the other three groups showed statistically significant levels of AF risk (ORs 1.07 (high risk, low dose), 1.06 (low risk, low dose) and 0.95 (low risk, high dose). Conclusion This meta-analysis suggests that treatment with EPA/DHA is most likely to increase risk for AF in patients at high-risk for CVD who are treated with high doses of EPA/DHA. The risk for AF should be balanced against the benefits of EPA/DHA in making treatment decisions.

There is growing evidence that optimising dietary quality and engaging in physical activity (PA) can reduce dementia and cognitive decline risk and improve psychosocial health and quality of life (QoL). Multimodal interventions focusing on diet and PA are recognised as significant strategies to tackle these behavioural risk factors; however, the cost-effectiveness of such interventions is seldom reported. A limited cost consequence based on a 12-month cluster-randomised Mediterranean diet (MedDiet) and walking controlled trial (MedWalk) was undertaken. In addition, QoL data were analysed. Programme costs ($AUD2024) covered staff to deliver the MedWalk programme and foods to support dietary behaviour change. The primary outcome measure of this study was change in QoL utility score, measured using the Assessment of Quality of Life (AQoL-8D). Change scores were compared for the groups using general linear models while controlling for demographic factors associated with baseline group differences and attrition. Change in QoL (decreased, maintained or improved) was determined using a cross-tabulation test. MedWalk programme costs were estimated at $2695 AUD per participant and control group cost at $165 per person - a differential cost of $2530. Mean change in utility scores from baseline to 12 months was not statistically significant between groups. Nevertheless, the MedWalk group was significantly less likely to experience a reduction in their QoL (20·3 % MedWalk v. 42·6 % control group) (P = 0·020). A MedDiet and walking intervention may have a role in preventing decline in QoL of older Australians; however, longer-term follow-up would be beneficial to see if this is maintained.

There is seasonal variability in the incidence of immune-related diseases among the general population. Data from two studies was evaluated to determine whether or not this seasonal variability is also present for ratings of immune fitness, i.e., the capacity of the body to respond to health challenges (such as infections) by activating an appropriate immune response, essential to maintain health, prevent and resolve disease, and improve quality of life. The first study comprises a between group comparison of participants that rated their past month’s immune fitness either in winter, spring or summer. The second longitudinal study comprised a within-subject comparison of participants that rated their momentary immune fitness two times in autumn, and subsequently in winter and summer. Both studies did not include any intervention. The analyses revealed no significant differences in immune fitness across the seasons. In conclusion, the impact of health challenges (e.g., the presence of rhinovirus or a greater pollen count) differs between seasons, and thereby can increase the chances of getting sick (e.g., common cold in winter or allergic rhinitis in spring). However, the data from the two studies presented here suggest that immune fitness does not vary across the seasons.

Berryfruit consumption has been shown to improve aspects of cognition in humans, and may protect against age-related cognitive decline via antioxidant mechanisms. This study investigated whether short-term supplementation with New Zealand 'Blackadder' blackcurrant (BC) juice supports spatial learning and memory in healthy young adult Sprague Dawley rats. Male rats (n = 24) received BC juice (n = 12; 5.4 mg/kg polyphenols) or a sugar-matched placebo (n = 12) prior to each daily trial during a four-day Morris Water Maze (MWM) acquisition phase and a probe trial on day five. BC supplementation significantly reduced cumulative distance (p = 0.020) and latency (p = 0.030) to the platform. In the probe trial, the trends showed that BC-supplemented rats spent more time in the platform zone. These improvements corresponded with detectable plasma anthocyanins, and trends toward higher hippocampal superoxide dismutase activity (p = 0.028, pa = 0.140) and lower circulating corticosterone (p = 0.052, pa = 0.228) in the BC group. These results suggest that BC phytochemicals may support spatial learning and memory. Mechanisms of effect may occur through specific antioxidant-mediated neuroprotective pathways and/or modulation of aspects of the hypothalamic-pituitary-adrenal axis.

The rising incidence of neurodegenerative diseases in an ageing global population has shifted research focus towards modifiable risk factors, such as diet. Despite potential links between dietary patterns and brain health, inconsistencies in neuroimaging outcomes underscore a gap in understanding how diet impacts brain ageing. This study explores the relationship between three dietary patterns - Mediterranean, Dietary Approaches to Stop Hypertension (DASH) and Mediterranean-DASH Intervention for Neurodegenerative Delay - and cognitive outcomes as well as brain connectivity. The study aimed to assess the association of these diets with brain structure and cognitive function, involving a middle-aged healthy group and an older cohort with subjective cognitive decline. The study included cognitive assessments and diffusion-weighted MRI data to analyse white matter microstructural integrity. Participants comprised fifty-five older individuals with subjective cognitive decline (54·5 % female, mean age = 64) and fifty-two healthy middle-aged individuals (48·1 % female, mean age = 53). Age inversely correlated with certain cognitive functions and global brain metrics, across both cohorts. Adherence to the Mediterranean, DASH and Mediterranean-DASH Intervention for Neurodegenerative Delay diets showed no significant cognitive or global brain metric improvements after adjusting for covariates (age, education, BMI). Network-based statistics analysis revealed differences in brain subnetworks based on DASH diet adherence levels in the subjective cognitive decline cohort. In the healthy cohort, lower white matter connectivity was associated with reduced adherence to Mediterranean-DASH Intervention for Neurodegenerative Delay and DASH diets. Ultimately, the study found no strong evidence connecting dietary patterns to cognitive or brain connectivity outcomes. Future research should focus on longitudinal studies and refine dietary assessments.

BACKGROUND:Milk fat globule membrane (MFGM) phospholipids have been linked to improved cognitive function, especially in infants, but evidence in healthy older adults is limited. OBJECTIVES:This project investigated MFGM phospholipid supplementation in older adults and focused on clinically meaningful cognitive function and other health-related outcomes. METHODS:This study was a multicenter, repeated-measures, parallel groups, randomized, double-blind, placebo-controlled trial. A total of N = 263 participants aged 55-75 y were randomly assigned to receive: 1) powdered milk fortified with low-dose MFGM (1.7-g phospholipid/d); 2) powdered milk fortified with high-dose MFGM (4.0-g phospholipid/d); or 3) rice starch powder (Control). Randomization used minimization to balance groups across study sites, sex, age, and Montreal Cognitive Assessment scores (MoCA). Participants consumed the product daily for 16 wk and attended their local study site at baseline, week 8, and endpoint. At each visit, they completed various cognitive, behavioral, biochemical, and physical measures. RESULTS:For the primary cognitive outcome, Repeatable Battery for Neuropsychological Status (RBANS), there were no significant treatment effects, nor for the secondary cognitive outcome, Computerized Mental Performance Assessment System (COMPASS); however, alertness (Bond-Lader Visual Analogue Scales) was better maintained during cognitive testing at endpoint in the high-dose group. TNF-α was reduced in the high-dose group, whereas γ-aminobutyric acid (GABA) and serotonin increased in both MFGM groups. Cholesterol and low-density lipoprotein (LDL) were also reduced in both MFGM groups. Active B12 increased, and homocysteine tended to decrease in the high-dose group. CONCLUSIONS:Although no significant effects were evident for cognitive function, subjective alertness during cognitive testing was improved in the high-dose group. Reduced inflammation, cholesterol, and LDL impacts for long-term cardiovascular health, linked with cognitive decline in aging. MFGM supplementation positively impacted active B12 (high and low dose) and homocysteine (high dose only), which have been associated with brain health. Longer study durations are needed to demonstrate cognitive benefits. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12620000270910; www.anzctr.org.au.

Compared with Panax ginseng (Asian ginseng), Panax quinquefolius (American ginseng) has received relatively little research attention. Nevertheless, across several clinical trials a common finding is that P. quinquefolius extracts improve aspects of mood, mental fatigue, and cognitive function. This review details the findings from double-blind, randomized, controlled clinical trials which included assessment of cognitive performance, fatigue, or mood, individually or in combination. Limited fatigue benefits were observed in cancer patients at high doses (2000mg). The most notable effects at lower doses (100mg-400 mg) included enhancement of attentional and working memory performance in healthy adults and in Schizophrenia patients. Several studies also highlighted potential mechanisms underlying the cognitive effects of P. quinquefolius. These include increased activation of frontoparietal neural circuits and, in the context of the gut-brain axis, alterations of the human gut microbiome composition. The effects are also consistent with cholinergic modulation. Such effects suggest that P. quinquefolius extract may have benefits to everyday cognitive function.