Tryptophan-enriched diet or 5-hydroxytryptophan supplementation given in a randomized controlled trial impacts social cognition on a neural and behavioral level.

Understanding of emotions and intentions are key processes in social cognition at which serotonin is an important neuromodulator. Its precursor is the essential amino acid tryptophan (TRP). Reduced TRP availability leads to weaker impulse control ability and higher aggression, while TRP supplementation promotes confidence. In a double-blind placebo-controlled fMRI study with 77 healthy adults, we investigated the influence of a 4 week TRP enriched diet and an acute 5-hydroxytryptophan (5-HTP) intake on two social-cognitive tasks, a moral evaluation and an emotion recognition task. With 5-HTP, immoral behavior without negative consequences was rated as more reprehensible. Additionally, during story reading, activation in insula and supramarginal gyrus was increased after TRP intake. No significant effects of TRP on emotion recognition were identified for the whole sample. Importantly, emotion recognition ability decreased with age which was for positive emotions compensated by TRP. Since the supramarginal gyrus is associated with empathy, pain and related information integration results could be interpreted as reflecting stricter evaluation of negative behavior due to better integration of information. Improved recognition of positive emotions with TRP in older participants supports the use of a TRP-rich diet to compensate for age related decline in social-cognitive processes.

Chinese herbal medicines for mild cognitive impairment: A protocol for meta-analysis and trial sequential analysis.

BACKGROUND: Mild cognitive impairment (MCI), as a common neurodegenerative aging disease representing an intermediate stage between normal cognitive functioning and dementia, poses an excessive burden on health care. The clinical benefit of Chinese herbal medicines (CHMs) for MCI remains inconclusive. This study is aimed at evaluating the efficacy and acceptability of CHMs through meta-analysis and trial sequential analysis (TSA). METHODS: We applied extensive strategies on preliminary literature screening to identify relevant randomized controlled trials which meticulously compare any of CHMs interventions with placebo groups as monotherapy for MCI. The primary outcome of this study is the change of global cognitive function, and the secondary outcomes include assessments of activities of daily living, mood, and adverse events. Data synthesis, risk of bias assessment, sensitivity and subgroup analyses, and TSA will be conducted with application of Review Manager, Stata, and TSA software. The quality of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation instrument. INPLASY registration number: INPLASY202190006 (https://inplasy.com/inplasy-2021-9-0006/). RESULTS: This study will confirm the clinical efficacy and safety of CHMs when used in the treatment of patients with MCI. CONCLUSION: This study will provide reliable evidence and references for the selection of CHMs in therapy and future clinical research of MCI.

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations.

The development of neuropathy and of mood alterations is frequent after chemotherapy. These complications, independent from the antitumoral mechanism, are interconnected due to an overlapping in their processing pathways and a common neuroinflammatory condition. This study aims to verify whether in mice the treatment with the proteasome inhibitor bortezomib (BTZ), at a protocol capable of inducing painful neuropathy, is associated with anxiety, depression and supraspinal neuroinflammation. We also verify if the therapeutic treatment with the antagonist of the prokineticin (PK) system PC1, which is known to contrast pain and neuroinflammation, can prevent mood alterations. Mice were treated with BTZ (0.4 mg/kg three times/week for 4 weeks); mechanical allodynia and locomotor activity were evaluated over time while anxiety (dark light and marble burying test), depression (sucrose preference and swimming test) and supraspinal neuroinflammation were checked at the end of the protocol. BTZ treated neuropathic mice develop anxiety and depression. The presence of mood alterations is related to the presence of neuroinflammation and PK system activation in prefrontal cortex, hippocampus and hypothalamus with high levels of PK2 and PKR2 receptor, IL-6 and TNF-α, TLR4 and an upregulation of glial markers. PC1 treatment, counteracting pain, prevented the development of supraspinal inflammation and depression-like behavior in BTZ mice.

Psychological and Antibacterial Effects of Footbath Using the Lindera umbellata Essential Oil.

Lindera umbellata (Lu) essential oil primarily contains linalool and has relaxation properties. We investigated the psychological and antibacterial effects of footbath with Lu essential oil. The participants included 20 women without medical history and received two intervention plans: footbath without any essential oil and footbath using Lu essential oil. Next, questionnaires regarding impressions and mood states were provided for them to answer. In addition, their autonomic nervous system activity was measured, and the aerobic viable of count on the feet was determined. The high-frequency value reflecting the parasympathetic nervous system activity significantly increased after footbath using Lu essential oil. In the questionnaire about the mood states, the subscale scores of tension-anxiety, depression, fatigue, and confusion after intervention were lower than those before intervention regardless of the use of the essential oil. Conversely, the anger-hostility score decreased only in the group using Lu essential oil. Furthermore, the decrease in aerobic viable count after intervention was not significantly different between the two groups. Footbath using Lu essential oil increased the parasympathetic nervous system activity and relieved anger. Taken together, we suggest that footbath using Lu essential oil has a relaxation effect.

Effects of Thai Local Ingredient Odorants, Litsea cubeba and Garlic Essential Oils, on Brainwaves and Moods.

The functional food market is growing with a compound annual growth rate of 7.9%. Thai food recipes use several kinds of herbs. Lemongrass, garlic, and turmeric are ingredients used in Thai curry paste. Essential oils released in the preparation step create the flavor and fragrance of the famous tom yum and massaman dishes. While the biological activities of these ingredients have been investigated, including the antioxidant, anti-inflammatory, and antimicrobial activities, there is still a lack of understanding regarding the responses to the essential oils of these plants. To investigate the effects of essential oil inhalation on the brain and mood responses, electroencephalography was carried out during the non-task resting state, and self-assessment of the mood state was performed. The essential oils were prepared in several dilutions in the range of the supra-threshold level. The results show that Litsea cubeba oil inhalation showed a sedative effect, observed from alpha and beta wave power reductions. The frontal and temporal regions of the brain were involved in the wave alterations. Garlic oil increased the alpha wave power at lower concentrations; however, a sedative effect was also observed at higher concentrations. Lower dilution oil induced changes in the fast alpha activity in the frontal region. The alpha and beta wave powers were decreased with higher dilution oils, particularly in the temporal, parietal, and occipital regions. Both Litsea cubeba and turmeric oils resulted in better positive moods than garlic oil. Garlic oil caused more negative moods than the others. The psychophysiological activities and the related brain functions require further investigation. The knowledge obtained from this study may be used to design functional food products.

Creatine Supplementation in Women's Health: A Lifespan Perspective.

Despite extensive research on creatine, evidence for use among females is understudied. Creatine characteristics vary between males and females, with females exhibiting 70-80% lower endogenous creatine stores compared to males. Understanding creatine metabolism pre- and post-menopause yields important implications for creatine supplementation for performance and health among females. Due to the hormone-related changes to creatine kinetics and phosphocreatine resynthesis, supplementation may be particularly important during menses, pregnancy, post-partum, during and post-menopause. Creatine supplementation among pre-menopausal females appears to be effective for improving strength and exercise performance. Post-menopausal females may also experience benefits in skeletal muscle size and function when consuming high doses of creatine (0.3 g·kg-1·d-1); and favorable effects on bone when combined with resistance training. Pre-clinical and clinical evidence indicates positive effects from creatine supplementation on mood and cognition, possibly by restoring brain energy levels and homeostasis. Creatine supplementation may be even more effective for females by supporting a pro-energetic environment in the brain. The purpose of this review was to highlight the use of creatine in females across the lifespan with particular emphasis on performance, body composition, mood, and dosing strategies.

Modafinil Decreased Thalamic Activation in Auditory Emotional Processing: A Randomized Controlled Functional Magnetic Resonance Imaging Study.

BACKGROUND: Modafinil improves wakefulness and attention, is approved in Japan for treatment of narcolepsy, and was reported to be effective for attention-deficit/hyperactivity disorder. However, it was reported to induce emotional instability, including mania, depression, and suicidal ideation. Such side effects may be related to changes in cognitive behavior caused by the effects of modafinil on emotional recognition. However, the effects of modafinil on the neural basis of emotional processing have not been fully verified. We used functional magnetic resonance imaging to investigate the effects of modafinil on the neural basis of auditory emotional processing. METHODS: This study adopted a placebo-controlled within-subject crossover design. Data from 14 participants were analyzed. The effects of modafinil on cerebral activation and task performance during an emotional judgement task were analyzed. RESULTS: Task accuracy decreased significantly and response time of emotional judgement was significantly delayed by modafinil, as compared with placebo. Right thalamic activation in auditory emotional processing was significantly less in the modafinil condition than in the placebo condition. In addition, reduction of right thalamic activation by modafinil was positively correlated with accuracy of emotional judgement. CONCLUSIONS: Our findings suggest that modafinil acts on the right thalamus and changes behavior and brain function associated with auditory emotional processing. These results indicate that modafinil might change emotional recognition by reducing emotional activation related to social communication.

Effects of 12 Weeks Cosmos caudatus Supplement among Older Adults with Mild Cognitive Impairment: A Randomized, Double-Blind and Placebo-Controlled Trial.

Cosmos caudatus (CC) contains high flavonoids and might be beneficial in neuroprotection. It has the potential to prevent neurodegenerative diseases. Therefore, we aimed to investigate the effects of 12 weeks of Cosmos caudatus supplement on cognitive function, mood status, blood biochemical profiles and biomarkers among older adults with mild cognitive impairment (MCI) through a double-blind, placebo-controlled trial. The subjects were randomized into CC supplement (n = 24) and placebo group (n = 24). Each of them consumed one capsule of CC supplement (250 mg of CC/capsule) or placebo (500 mg maltodextrin/capsule) twice daily for 12 weeks. Cognitive function and mood status were assessed at baseline, 6th week, and 12th week using validated neuropsychological tests. Blood biochemical profiles and biomarkers were measured at baseline and 12th week. Two-way mixed analysis of variance (ANOVA) analysis showed significant improvements in mini mental state examination (MMSE) (partial η2 = 0.150, p = 0.049), tension (partial η2 = 0.191, p = 0.018), total mood disturbance (partial η2 = 0.171, p = 0.028) and malondialdehyde (MDA) (partial η2 = 0.097, p = 0.047) following CC supplementation. In conclusion, 12 weeks CC supplementation potentially improved global cognition, tension, total mood disturbance, and oxidative stress among older adults with MCI. Larger sample size and longer period of intervention with incorporation of metabolomic approach should be conducted to further investigate the underlying mechanism of CC supplementation in neuroprotection.

5HT-2C agonist lorcaserin decreases cannabis self-administration in daily cannabis smokers.

There are no FDA-approved treatments for cannabis use disorder (CUD). Preclinical research has shown that the 5HT-2C agonist lorcaserin attenuates cue-induced reinstatement of THC seeking and self-administration. The goal of this placebo-controlled, counterbalanced, within-subject human laboratory study was to examine lorcaserin's effects on cannabis intoxication and self-administration. Lorcaserin (10 mg BID) was administered during one of two 13-day inpatient phases and placebo during the other; each phase was separated by ≥7 days of washout. Inpatient phases comprised (1) standardized cannabis administration (7.0% THC) at no financial cost (intoxication), counterbalanced with (2) the option to self-administer cannabis following either 0 or 3 days of abstinence. Cognitive task performance, food intake, subjective ratings of drug effects, objective/subjective sleep measures, and tobacco cigarette use were also assessed. Fifteen normal-weight, daily cannabis users (4F, 11M) not seeking treatment for CUD completed the study. Lorcaserin significantly reduced cannabis self-administration following 0 and 3 days of cannabis abstinence and also reduced craving for cannabis during abstinence. Lorcaserin produced small but significant increases in positive cannabis ratings and body weight relative to placebo. Lorcaserin also reduced tobacco cigarette smoking on days of cannabis administration relative to placebo. During abstinence, subjective but not objective measures of sleep quality worsened during lorcaserin maintenance. Overall, lorcaserin's ability to decrease drug taking and cannabis craving in nontreatment-seeking cannabis users supports further investigation of 5HT-2C agonists as potential pharmacotherapies for CUD.

Effects of High-Dose, Short-Duration ß-Alanine Supplementation on Cognitive Function, Mood, and Circulating Brain-Derived Neurotropic Factor (BDNF) in Recreationally-Active Males Before Simulated Military Operational Stress.

Introduction: ß-alanine (BA) supplementation may improve cognition and mitigate symptoms of anxiety and depression associated with aging, neurological disorders, and physical exertion, which has been attributed to increases in brain carnosine and/or brain-derived neurotropic factor (BDNF). BA also provides beneficial effects on cognition, mood, and physical performance during military operations; however, whether BA can attenuate mood disruptions and cognitive dysfunction associated with the anticipatory stress prior to simulated military operations is unknown.Purpose: The present study examined the effects of 14 days of BA (12 g·day-1) supplementation on cognitive function, mood, and circulating BDNF concentrations in recreationally-active, healthy males with limited inflammation and oxidative stress prior to a 24h simulated military operation.Methods: Participants were randomized into BA (n = 10) or placebo (n = 9; PL) for 14 days. Cognitive function, mood, and circulating BDNF were assessed before (PRE) and after (POST) supplementation. Cognition was assessed via multiple object tracking (Neurotracker™), visuomotor reaction time (Dynavision™), mathematical processing (Serial Subtraction Test), and neuropsychological assessments (ANAM™). Mood was assessed using the Profile of Mood States (POMS) questionnaire. After POST testing, subjects underwent a 24h simulated military operation.Results: No change in measures of cognitive function or BDNF concentrations were observed (p > 0.05). However, BA experienced significant reductions (p = 0.046) in subjective feelings of depression, while PL experienced significant reductions (p = 0.021) in feelings of vigor from PRE to POST.Conclusions: High-dose, short-duration BA supplementation does not appear to affect cognitive function or circulating BDNF, but may mitigate the onset of negative mood states in healthy, recreationally-active males prior to a simulated military operation.

A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning.

L-tryptophan (TRP), one of the essential amino acids in humans, is a precursor of serotonin, and hence its intake is closely related to the suppression of depressed and anxious moods. We did a systematic review of RCTs to examine the effects of tryptophan intake on the mood of healthy adults by searching PubMed, the Cochrane Library, and Ichu-shi according to PRISMA guidelines. As a result, 11 RCTs met the criteria and were accepted. Four RCTs showed the effects of tryptophan intake on negative feelings and happy feelings in healthy individuals, with significant differences between the treatment and the control groups. This suggests that TRP intake may be an effective approach to decrease anxiety and increase positive mood in healthy individuals. On the other hand, the effectiveness of TRP for aggressive feelings was not recognized. Reviewing these 11 RCTs, we concluded that taking 0.14-3 g of TRP per day in addition to the usual meal can be expected to improve the mood of healthy individuals. In order to estimate the optimum amount of TRP intake more accurately, further studies need to be conducted with more appropriate settings of intake period, intake frequency, and intake method.

The Effects of Vitamin D-Enriched Mushrooms and Vitamin D3 on Cognitive Performance and Mood in Healthy Elderly Adults: A Randomised, Double-Blinded, Placebo-Controlled Trial.

Despite abundant cross-sectional evidence that low vitamin D status is associated with risk of cognitive decline in ageing, interventional evidence for benefits of vitamin D supplementation is lacking. This study was a 6 month randomised, double-blinded placebo-controlled clinical trial of the effects of vitamin D3 (D3), enhanced vitamin D2 in a mushroom matrix (D2M), standard mushroom (SM) and placebo (PL) on cognition and mood in n = 436 healthy older male (49%) and female volunteers aged ≥ 60 years. Primary end points were change in serum vitamin D metabolites (25-OH-D, 25-OH-D2 and 25-OH-D3), cognitive performance, and mood over 24 weeks. Levels of total 25-OH-D and 25-OH-D3 were maintained in the D3 arm but decreased significantly (p < 0.05) in the remaining arms (D2M, SM and PL). Analysis also revealed differential changes in these metabolites depending on total vitamin D status at baseline. There were no significant effects of treatment on any of the measures of cognitive function or mood. Overall, the results show that daily supplementation of ~600 IU of vitamin D3 was sufficient to maintain 25-OH-D throughout winter months, but in contrast to existing cross-sectional studies there was no support for benefit of vitamin D supplementation for mood or cognition in healthy elderly people.

The Possible Importance of Glutamine Supplementation to Mood and Cognition in Hypoxia from High Altitude.

Hypoxia induced by low O2 pressure is responsible for several physiological and behavioral alterations. Changes in physiological systems are frequent, including inflammation and psychobiological declines such as mood and cognition worsening, resulting in increased reaction time, difficulty solving problems, reduced memory and concentration. The paper discusses the possible relationship between glutamine supplementation and worsening cognition mediated by inflammation induced by high altitude hypoxia. The paper is a narrative literature review conducted to verify the effects of glutamine supplementation on psychobiological aspects. We searched MEDLINE/PubMed and Web of Science databases and gray literature by Google Scholar for English articles. Mechanistic pathways mediated by glutamine suggest potential positive effects of its supplementation on mood and cognition, mainly its potential effect on inflammation. However, clinical studies are scarce, making any conclusions impossible. Although glutamine plays an important role and seems to mitigate inflammation, clinical studies should test this hypothesis, which will contribute to a better mood and cognition state for several people who suffer from problems mediated by hypoxia.

Flavonoids as therapeutic candidates for emotional disorders such as anxiety and depression.

Emotional disorders such as anxiety and depression are widespread psychological diseases that affect up to 20% of the world's population. There are many approaches to the discovery of novel agents for the treatment of depressive- and anxiety-like symptoms. However, the efficacy of existing drugs for emotional disorders is only exerted after a few weeks of treatment and have serious side effects. Due to this, new strategies to find suitable and safe options are being sought by many researchers. Among them, a lot of interest has been attracted by plant-derived natural compounds due to their wide range of beneficial effects for new agent development. Flavonoids are natural polyphenol-like compounds found commonly in plants, fruits, vegetables, and medicinal herbs. A diverse range of flavonoids have been studied to investigate their potential therapeutic activities for the treatment of brain-associated disorders, including anxiety and depression. The main aim of this review is to understand the associations between the various flavonoids and the emotional disorders and discuss the therapeutic effects of these natural compounds that were demonstrated during the conduction of recent studies. The current work shows advances in the latest research of some flavonoids as a potential candidate for the treatment of emotional disorders. We summarize their behavioral, molecular, physiological, and neurochemical effects in various in vitro and in vivo models. Therefore, in the present work, the latest studies were collected on the most important flavonoid compounds and their underlying mechanisms of action in emotion-related disorders were discussed.

The effects of six months Persicaria minor extract supplement among older adults with mild cognitive impairment: a double-blinded, randomized, and placebo-controlled trial.

BACKGROUND: Persicaria minor extract exhibits antioxidant and anti-inflammatory properties and has potential effects on cognitive function and mood. However, the effects of P.minor on brain activation and biomarkers have not been studied among older adults. This multicentre, randomized, double-blinded, placebo-controlled study aimed to investigate the effect of 6 months P.minor extract supplement (Biokesum®) on cognition, mood, biomarkers, and brain activation among older adults with Mild Cognitive Impairment (MCI). METHOD: A total of 36 Malaysian community-dwelling older adults with MCI (60-75-year-old) were randomized into Biokesum® (n = 18) and placebo group (n = 18). Each subject consumed one capsule of Biokesum® (250 mg/capsule) or placebo (maltodextrin, 280 mg/capsule) twice daily for 6 months. Cognitive function and mood were assessed at baseline, 3rd, and 6th-month using neuropsychological tests (MMSE, Digit Span, RAVLT, Digit Symbol, and Visual Reproduction) and Profile of Mood State (POMS) questionnaire. Blood lipid profile, fasting blood glucose, and biomarkers (MDA, LPO, COX-2, iNOS, and BDNF) were measured at baseline and 6th month. By the end of the intervention, there were 30 compliers (Biokesum®: N = 15; Placebo: N = 15) and 6 dropouts. For brain activation assessment, 15 subsamples (Biokesum®: N = 8; Placebo: N = 7) completed N-back and Stroop tasks during fMRI scanning at baseline and 6th month. The dorsolateral prefrontal cortex (Brodmann's area 9 and 46) was identified as a region of interest (ROI) for brain activation analysis using SPM software. RESULTS: Two-way mixed ANOVA analysis showed significant improvements in Visual Reproduction II (p = 0.012, partial η2 = 0.470), tension (p = 0.042, partial η2 = 0.147), anger (p = 0.010, partial η2 = 0.207), confusion (p = 0.041, partial η2 = 0.148), total negative subscales (p = 0.043, partial η2 = 0.145), BDNF (p = 0.020, partial η2 = 0.179) and triglyceride (p = 0.029, partial η2 = 0.237) following 6 months of Biokesum® supplementation. Preliminary finding also demonstrated significant improvement at 0-back task-induced right DLPFC activation (p = 0.028, partial η2 = 0.652) among subsamples in Biokesum® group. No adverse events were reported at the end of the study. CONCLUSION: Six months Biokesum® supplementation potentially improved visual memory, negative mood, BDNF, and triglyceride levels among older adults with MCI. Significant findings on brain activation at the right DPLFC must be considered as preliminary. TRIAL REGISTRATION: Retrospectively registered on 30th August 2019 [ ISRC TN12417552 ].

An Exploratory Analysis of Changes in Mental Wellbeing Following Curcumin and Fish Oil Supplementation in Middle-Aged and Older Adults.

Curcumin has previously been shown to enhance mood in non-depressed older adults. However, observed benefits were limited to short-term supplementation (4 weeks). In a 16 week randomized, double-blind, placebo-controlled, 2 × 2 factorial design trial, we supplemented overweight or obese non-depressed adults (50-80 years) with curcumin (160 mg/day), fish oil (2000 mg docosahexaenoic acid +400 mg eicosapentaenoic acid/day), or a combination of both. Secondary outcomes included mental wellbeing measures (mood states and subjective memory complaints (SMCs)) and quality of life (QoL). Furthermore, plasma apolipoprotein E4 (APOE4) was measured to determine whether APOE4 status influences responses to fish oil. Curcumin improved vigour (p = 0.044) compared to placebo and reduced SMCs compared to no curcumin treatment (p = 0.038). Fish oil did not affect any mood states, SMCs or QoL; however, responses to fish oil were affected by APOE4 status. In APOE4 non-carriers, fish oil increased vigour (p = 0.030) and reduced total mood disturbances (p = 0.048) compared to placebo. Improvements in mental wellbeing were correlated with increased QoL. Combining curcumin with fish oil did not result in additive effects. This exploratory analysis indicates that regular supplementation with either curcumin or fish oil (limited to APOE4 non-carriers) has the potential to improve some aspects of mental wellbeing in association with better QoL.

The Effect of Long-Term Aronia melanocarpa Extract Supplementation on Cognitive Performance, Mood, and Vascular Function: A Randomized Controlled Trial in Healthy, Middle-Aged Individuals.

Cognitive decline is associated with lifestyle-related factors such as overweight, blood pressure, and dietary composition. Studies have reported beneficial effects of dietary anthocyanins on cognition in older adults and children. However, the effect of anthocyanin-rich Aronia melanocarpa extract (AME) on cognition is unknown. Therefore, this study aimed to determine the effect of long-term supplementation with AME on cognitive performance, mood, and vascular function in healthy, middle-aged, overweight adults. In a randomized double-blind placebo-controlled parallel study, 101 participants either consumed 90 mg AME, 150 mg AME, or placebo for 24 weeks. The grooved pegboard test, number cross-out test, and Stroop test were performed as measures for psychomotor speed, attention, and cognitive flexibility. Mood was evaluated with a visual analogue scale, serum brain-derived neurotrophic factor (BDNF) was determined, and vascular function was assessed by carotid ultrasounds and blood pressure measurements. AME improved psychomotor speed compared to placebo (90 mg AME: change = -3.37; p = 0.009). Furthermore, 150 mg AME decreased brachial diastolic blood pressure compared to 90 mg AME (change = 2.44; p = 0.011), but not compared to placebo. Attention, cognitive flexibility, BDNF, and other vascular parameters were not affected. In conclusion, AME supplementation showed an indication of beneficial effects on cognitive performance and blood pressure in individuals at risk of cognitive decline.

A Randomized, Crossover Study of the Acute Cognitive and Cerebral Blood Flow Effects of Phenolic, Nitrate and Botanical Beverages in Young, Healthy Humans.

BACKGROUND: In whole foods, polyphenols exist alongside a wide array of other potentially bioactive phytochemicals. Yet, investigations of the effects of combinations of polyphenols with other phytochemicals are limited. OBJECTIVE: The current study investigated the effects of combining extracts of beetroot, ginseng and sage with phenolic-rich apple, blueberry and coffee berry extracts. DESIGN: This randomized, double-blind, placebo-controlled crossover design investigated three active beverages in 32 healthy adults aged 18-49 years. Each investigational beverage comprised extracts of beetroot, ginseng and sage. Each also contained a phenolic-rich extract derived from apple (containing 234 mg flavanols), blueberry (300 mg anthocyanins) or coffee berry (440 mg chlorogenic acid). Cognition, mood and CBF parameters were assessed at baseline and then again at 60, 180 and 360 min post-drink. RESULTS: Robust effects on mood and CBF were seen for the apple and coffee berry beverages, with increased subjective energetic arousal and hemodynamic responses being observed. Fewer effects were seen with the blueberry extract beverage. CONCLUSIONS: Either the combination of beetroot, ginseng and sage was enhanced by the synergistic addition of the apple and coffee berry extract (and to a lesser extent the blueberry extract) or the former two phenolic-rich extracts were capable of evincing the robust mood and CBF effects alone.

Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial.

Importance: Low levels of 25-hydroxyvitamin D have been associated with higher risk for depression later in life, but there have been few long-term, high-dose large-scale trials. Objective: To test the effects of vitamin D3 supplementation on late-life depression risk and mood scores. Design, Setting, and Participants: There were 18 353 men and women aged 50 years or older in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized clinical trial of cardiovascular disease and cancer prevention among 25 871 adults in the US. There were 16 657 at risk for incident depression (ie, no depression history) and 1696 at risk for recurrent depression (ie, depression history but no treatment for depression within the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017, and this was the final date of follow-up. Intervention: Randomized assignment in a 2 × 2 factorial design to vitamin D3 (2000 IU/d of cholecalciferol) and fish oil or placebo; 9181 were randomized to vitamin D3 and 9172 were randomized to matching placebo. Main Outcomes and Measures: The primary outcomes were the risk of depression or clinically relevant depressive symptoms (total of incident and recurrent cases) and the mean difference in mood scores (8-item Patient Health Questionnaire depression scale [PHQ-8]; score range, 0 points [least symptoms] to 24 points [most symptoms]; the minimal clinically important difference for change in scores was 0.5 points). Results: Among the 18 353 randomized participants (mean age, 67.5 [SD, 7.1] years; 49.2% women), the median treatment duration was 5.3 years and 90.5% completed the trial (93.5% among those alive at the end of the trial). Risk of depression or clinically relevant depressive symptoms was not significantly different between the vitamin D3 group (609 depression or clinically relevant depressive symptom events; 12.9/1000 person-years) and the placebo group (625 depression or clinically relevant depressive symptom events; 13.3/1000 person-years) (hazard ratio, 0.97 [95% CI, 0.87 to 1.09]; P = .62); there were no significant differences between groups in depression incidence or recurrence. No significant differences were observed between treatment groups for change in mood scores over time; mean change in PHQ-8 score was not significantly different from zero (mean difference for change in mood scores, 0.01 points [95% CI, -0.04 to 0.05 points]). Conclusions and Relevance: Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with vitamin D3 compared with placebo did not result in a statistically significant difference in the incidence and recurrence of depression or clinically relevant depressive symptoms or for change in mood scores over a median follow-up of 5.3 years. These findings do not support the use of vitamin D3 in adults to prevent depression. Trial Registration: ClinicalTrials.gov Identifiers: NCT01169259 and NCT01696435.