Effect of kava (Piper methysticum) on peripheral gene expression among individuals with generalized anxiety disorder: A post hoc analysis of a randomized controlled trial.

Kava is a South Pacific plant-based medicine with anxiolytic properties, but little is known about the impact kava has on gene expression or whether gene expression can serve as a marker of kava response. This study aimed to determine whether kava treatment alters the expression of genes with physiological relevance to anxiety pathophysiology and whether the baseline expression of these physiologically relevant genes modifies the efficacy of kava treatment. In this post hoc analysis, we examined the expression of 48 genes relevant to the pathophysiology of anxiety collected from a double-blind randomized controlled trial that assessed the efficacy of kava treatment in generalized anxiety disorder. Peripheral blood gene expression was measured in 71 (34 kava, 37 placebo) adults at baseline and in 40 (19 kava, 21 placebo) after 8 weeks of treatment by reverse transcription polymerase chain reaction (PCR). Results revealed that kava decreased the expression of a subunit of the GABAA -rho receptor gene (GABRR2) and catechol-O-methyltransferase (COMT), a gene related to catecholamine metabolism. Kava efficacy was not found to be modified by baseline (pretreatment) expression of relevant genes. Although these results did not withstand statistical correction for multiple comparisons and require external validation, they support the notion that kava's mechanism of action includes interaction with GABAergic and catecholaminergic systems.

Effects of Bacopa monnieri (CDRI 08®) in a population of males exhibiting inattention and hyperactivity aged 6 to 14 years: A randomized, double-blind, placebo-controlled trial.

The current study investigated the efficacy of extract of Bacopa monnieri (BM; CDRI 08®) in reducing levels of inattention and hyperactivity in young children. BM has demonstrated improvements in cognitive outcomes in adults, yet little research is available on its effects in younger populations. A 14-week randomized, double-blind, placebo-controlled clinical trial, with placebo run-in and run-out phases, investigated the effects of BM on behavioural, cognitive, mood, and sleep effects in male children aged 6 to 14 years against placebo. One-hundred and twelve participants were recruited into the trial, with 93 datasets available for analysis. No significant behavioural differences were noted between treatment groups. Cognitive outcomes indicated decreased error-making in children taking CDRI 08® (p = .04) and increased speed of reaction time in those taking placebo (p = .04) at study end. Improvements in cognitive flexibility (p = .01), executive functioning (p = .04), interpersonal problems (p = .02), and sleep routine (p = .04) were noted in those consuming CDRI 08® over placebo. CDRI 08® did not improve behavioural outcomes, but may have cognitive, mood and sleep benefits in children aged 6 to 14 years. Further study is required to support the findings presented here.

Higher habitual dietary flavonoid intake associates with lower central blood pressure and arterial stiffness in healthy older adults.

Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 (sd 4·1) years; BMI, 26·4 (sd 4·41) kg/m2; 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd/d higher intake of anthocyanins ((sd 44·3) mg/d) was associated with significantly lower cDBP (-1·56 mmHg, 95 % CI -2·65, -0·48) and cMAP (-1·62 mmHg, 95 % CI -2·82, -0·41). Similarly, each sd/d higher intake of flavanones ((sd 19·5) mg/d) was associated with ~1 % lower cAIx (-0·93 %, 95 % CI -1·77, -0·09). These associations remained significant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness; these findings require corroboration in further research.

The Relationship between Oxidative Stress and Anxiety in a Healthy Older Population.

Background/study context: F2-Isoprostanes are putative markers of oxidative stress, one of the processes associated with biological senescence. Evidence exists for elevated F2-Isoprostanes in chronic conditions including psychiatric disorders. Few studies have examined the relationship between oxidative stress and mood in older healthy samples, to establish the influence on mental health. Given current aging demographics in many nations, management of brain and mental health is crucial for longevity, chronic disease management, and quality of life.Method: We investigated the relationship between F2-Isoprostanes, a marker for oxidative stress, and anxiety and mood in 262 healthy adults aged 60-75 years, using baseline data from the Australian Research Council Longevity Intervention (ARCLI; ANZCTR12611000487910), a 12-month nutraceutical intervention study.Results: Higher F2 levels significantly predicted increased Depression-dejection and Anger-hostility subscale scores from the Profile of Mood States (POMS). Fatigue-inertia subscale was predicted by increased Body Mass Index. Spielberger State-Trait Inventory (STAI) scores were significantly higher in females.Conclusion: While the primary outcome data did not find a definitive relationship between F2 and total mood or general anxiety levels, the sub-scale data adds weight toward growing literature that biological processes such as oxidative stress are in part related to mood. This is a modifiable risk factor contributing to physical and mental wellbeing that are crucial to healthy aging.

Neurotrophins as a reliable biomarker for brain function, structure and cognition: A systematic review and meta-analysis.

Neurotrophins are signalling molecules involved in the formation and maintenance of synapses in the brain. They can cross the blood-brain barrier and be detected in peripheral blood, suggesting they may be a potential biomarker for brain health and function. In this review, the available literature was systematically searched for studies comparing peripheral neurotrophins levels with MRI and cognitive measures in healthy adults. Twenty-four studies were identified, six of which included a neuroimaging outcome. Fifteen studies measuring cognition were eligible for meta-analysis. The majority of studies measured levels of brain-derived neurotrophic factor (BDNF), with few assessing other neurotrophins. Results revealed BDNF is related to some neuroimaging outcomes, with some studies suggesting older age may be an important factor. A higher proportion of studies who had older samples observed significant effects between cognition and neurotrophin levels. When cognitive studies were pooled together in a meta-analysis, there was a weak non-significant effect between BDNF and cognitive outcomes. There was also a high level of heterogeneity between cognitive studies. Results indicated that gender was a notable source of the heterogeneity, but additional studies employing relevant covariates are necessary to better characterise the inter-relationship between circulating neurotrophins and cognition.

EPA and DHA as markers of nutraceutical treatment response in major depressive disorder.

PURPOSE: Depression clinical trials are increasingly studying biomarkers to predict and monitor response to treatment. Assessment of biomarkers may reveal subsets of patients who are responsive to nutraceutical treatment, which may facilitate a personalized approach to treating depression. METHODS: This is a post hoc analysis of an 8-week, double-blind, randomized, controlled trial (n = 158) investigating a combination nutraceutical comprising Omega-3 (EPA 1 g/DHA 656 mg), SAMe, zinc, 5-HTP, folinic acid, and co-factors versus placebo for the treatment of Major Depressive Disorder. The study explored levels of polyunsaturated fatty acids, folate, vitamin B12, zinc, homocysteine, and BDNF as possible predictors and correlates of response to nutraceutical supplementation. RESULTS: Concentrations of EPA and DHA in red cell membranes increased in response to treatment and were significantly correlated with a decrease in depressive symptoms during active treatment (p = 0.003 and p = 0.029; respectively). Higher baseline levels of omega-6 fatty acid also correlated with depression reduction in the active treatment group ( p = 0.011). No other biomarkers were associated with a lessening of depressive symptoms. CONCLUSION: Changes in fatty acid levels resulting from a nutraceutical combination containing EPA and DHA provide a response biomarker in treating depression.

Kava for generalised anxiety disorder: A 16-week double-blind, randomised, placebo-controlled study.

OBJECTIVE: Previous randomised, double-blind, placebo-controlled studies have shown that Kava (a South Pacific medicinal plant) reduced anxiety during short-term administration. The objective of this randomised, double-blind, placebo-controlled study was to perform a larger, longer-term trial assessing the efficacy and safety of Kava in the treatment of generalised anxiety disorder and to determine whether gamma-aminobutyric acid transporter (SLC6A1) single-nucleotide polymorphisms were moderators of response. METHODS: The trial was a phase III, multi-site, two-arm, 16-week, randomised, double-blind, placebo-controlled study investigating an aqueous extract of dried Kava root administered twice per day in tablet form (standardised to 120 mg of kavalactones twice/day) in 171 currently non-medicated anxious participants with diagnosed generalised anxiety disorder. The trial took place in Australia. RESULTS: An analysis of 171 participants revealed a non-significant difference in anxiety reduction between the Kava and placebo groups (a relative reduction favouring placebo of 1.37 points; p = 0.25). At the conclusion of the controlled phase, 17.4% of the Kava group were classified as remitted (Hamilton Anxiety Rating Scale score < 7) compared to 23.8% of the placebo group (p = 0.46). No SLC6A1 polymorphisms were associated with treatment response, while carriers of the rs2601126 T allele preferentially respond to placebo (p = 0.006). Kava was well tolerated aside from poorer memory (Kava = 36 vs placebo = 23; p = 0.044) and tremor/shakiness (Kava = 36 vs placebo = 23; p = 0.024) occurring more frequently in the Kava group. Liver function test abnormalities were significantly more frequent in the Kava group, although no participant met criteria for herb-induced hepatic injury. CONCLUSION: While research has generally supported Kava in non-clinical populations (potentially for more 'situational' anxiety as a short-term anxiolytic), this particular extract was not effective for diagnosed generalised anxiety disorder.

The Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910) addendum: neuroimaging and gut microbiota protocol.

BACKGROUND: The Australian Research Council Longevity Intervention (ARCLI) was designed to investigate the effects of two active supplements, Pycnogenol and Bacopa monnieri (CDRI08) on cognitive performance in a cohort of elderly participants. An additional antioxidant supplement has been included into the trial. A neuroimaging component has also been added to the ARCLI study to investigate the neurochemical biomarkers of oxidative stress in vivo, as well as structural and functional changes associated with ageing and oxidative stress. Faecal biomarkers of gut microflora will also be analysed to investigate if gut microbiota are associated with domains of cognition (e.g., attention, processing speed, memory), mood or other ARCLI outcome variables. The aim of this paper is to update the published methods of the ARCLI clinical trial before it is completed, and data analysis commences. METHODS: ARCLI is a randomised, placebo controlled, double-blind, now 4-arm clinical trial including neuroimaging and gut microflora sub-studies. Along with the demographic, haematological, mood, cardiovascular and cognitive assessments described in the initial protocol, 80 eligible participants from the overall study pool of ~ 400 will be recruited into the neuroimaging study and undergo scans at baseline, 3 months and 12 months. Proton magnetic resonance spectroscopy, resting state functional connectivity and arterial spin labelled perfusion sequences are neuroimaging techniques included for each MRI visit in the study. Similarly, approximately 300 participants from the main study pool will be recruited to provide faecal samples at baseline, 3 months and 12 months so that the gut microbiome can be studied. DISCUSSION: ARCLI is 12-month intervention study, currently underway with a group of older adults, investigating a range of outcomes and their association with ageing. The additional measurements in the ARCLI trial will further the understanding of the underlying mechanisms associated with healthy ageing and may provide insights into novel preventative therapeutic strategies for maintaining cognitive and brain health into old age. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000487970 .

Increases in total cholesterol and low density lipoprotein associated with decreased cognitive performance in healthy elderly adults.

The current study examined associations between blood lipid profiles and cognitive functioning using a healthy non-demented elderly sample. The sample comprised 196 healthy volunteers (male; 86: female 110) aged 60-75 years from the Australian Research Council Longevity Intervention (ARCLI) study cohort. Serum total cholesterol (T-C), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c) and triglycerides (TGL) were collected, and participants completed the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB). In line with prediction, higher levels of T-C and LDL-c were found to be associated with impaired speeds of response in tasks assessing recognition memory, working memory and inhibitory processing. However, contrary to prediction both TGL and HDL-c were found to be unrelated to cognitive functioning in the current sample. It is suggested that frontal lobe function may be differentially sensitive to the effects of T-C and LDL-c accumulation during the aging process. Future data collection as part of the larger ARCLI intervention study will provide important follow-up data regarding the ability of the baseline blood lipid data to predict subsequent cognitive change.

When should the driver with a history of substance misuse be allowed to return to the wheel? A review of the substance misuse section of the Australian national guidelines.

Assessing fitness to drive in applicants with a historical or current substance use disorder presents a specific clinical challenge. The Australian guidelines require evidence of remission and absence of cognitive change when considering applications for re-licensing driver or individuals applying to reengage in safety-sensitive work. This paper reviews some of the clinical and biochemical indicators that determine whether a particular person is in 'remission' and meets the criteria for return to driving or other safety-sensitive occupation. It provides an overview of the challenges in establishing an evidence-based approach to determining fitness for safety critical activities. There is no internationally accepted definition of 'remission'. Review of the literature and examination of assessment protocols from other national jurisdictions are available for alcohol and the more important drugs of interest in road safety. Assessing fitness to drive when there is a history of substance misuse and/or substance use disorders is a complex issue that requires assessment of biomarkers, clinical findings and clinical assessment before the person returns to driving. We propose that hair testing provides a reliable and reproducible way to demonstrate remission and provide cost-effective monitoring. Standardised psychological tests could provide a reproducible assessment of the cognitive effects of drug use and suitability to resume driving. We recommend that AustRoads amend the national guidelines to reflect an evidence-based approach to assessing fitness to drive after conviction for offences related to alcohol and drug use.

GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence.

Anxiety disorders are chronic and functionally disabling conditions with high psychological stress, characterised by cognitive symptoms of excessive worry and focus difficulties and physiological symptoms such as muscle tension and insomnia. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter within the central nervous system and is a key target of pharmacotherapies in the treatment of anxiety. Although current pharmaceutical treatments are often efficacious, they may cause undesirable side effects including cognitive decrements and withdrawal symptoms. Plant-based "phytomedicines" may provide novel treatment options, to act as an adjunctive or alternative to existing anxiolytic medications. As such, we conducted a systematic review to assess the current body of literature on anxiolytic phytomedicines and/or phytoconstituents. An open-ended search to 5 July 2017 was conducted using MEDLINE (PubMed), Scopus, and Cochrane library online databases and performed in a stepped format from preclinical to clinical investigations. Eligible studies must have had (a) in vitro evidence of GABA-modulating activity, (b) animal studies using anxiety models to test an anxiolytic effect, and (c) human clinical trials. Ten phytomedicines were identified as having preclinical investigations showing interaction with the GABA system, in addition to human clinical trials: kava, valerian, pennywort, hops, chamomile, Ginkgo biloba, passionflower, ashwagandha, skullcap, and lemon balm. Collectively, the literature reveals preclinical and clinical evidence for various phytomedicines modulating GABA-pathways, with comparative anxiolytic effect to the current array of pharmaceuticals, along with good safety and tolerability profiles.

The effect of a single dose of multivitamin and mineral combinations with and without guaraná on functional brain activity during a continuous performance task.

OBJECTIVES: Relatively few studies have explored the possibility of acute cognitive effects of multivitamin ingestion. This report explores the acute brain electrophysiological changes associated with multivitamin and mineral supplementation, with and without guaraná, using the steady-state visually evoked potential (SSVEP). METHODS: Based on the known SSVEP correlates of A-X continuous performance task (CPT) performance, and sensitivity to acute psychopharmacological manipulations, the A-X CPT was adopted as a task paradigm to explore treatment-related neurophysiological changes in attentional processing. Twenty healthy non-smoking adults aged 21-39 years (mean age = 28.35 years, SD = 5.52) took part in this double-blind, placebo-controlled, randomized, balanced crossover design study. RESULTS: The study demonstrated both transient and tonic changes in the SSVEP response during completion of the A-X CPT following multivitamin and mineral treatment both with and without guaraná. Transient changes in SSVEP response in prefrontal regions were observed after a single dose of a multivitamin and mineral preparation indicative of enhanced activity within brain regions engaged by the attentional demands of the task. This pattern of change in frontal regions was correlated with improved behavioural performance after treatment with the multivitamin and mineral combination. Where tonic shifts in SSVEP response were investigated, multivitamin and mineral treatment was associated with a pattern of increased inhibition across posterior regions, with enhanced excitatory processing in prefrontal regions. In contrast, multivitamin and mineral treatment with additional guaraná showed a tonic shift towards greater excitatory processes after a single treatment, consistent with the caffeine content of this treatment. DISCUSSION: While preliminary in nature, these findings suggest a single multivitamin/mineral dose is sufficient to impact on functional brain activity in task-related brain regions.

DSM-5 Tobacco Use Disorder and Sleep Disturbance: Findings from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III).

INTRODUCTION: The DSM-5 Tobacco use disorder diagnosis incorporates tobacco misuse, addictive behaviors and withdrawal symptomology. Tobacco use is bidirectionally associated with sleep pathology; however, no epidemiological studies have yet evaluated the associations between DSM-5 Tobacco use disorder and self-reported sleep disturbance. The current study aimed to evaluate health, medical and sleep-related factors among individuals within this diagnostic stratum. METHOD: A total of N = 36,177 adults who participated in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III) were included for analyses. The adjusted odd ratios (AOR) for individual classifications of DSM-5 Tobacco use disorder among those with subjective sleep disturbances were used as the primary outcome measure and relevant demographic, clinical and medical factors were considered in all univariate and multivariable analyses. RESULTS: Current and lifetime DSM-5 tobacco use disorder diagnoses were associated with poorer health and medical outcomes and higher rates of subjective sleep disturbances (all p < 0.001). Associations between current and lifetime DSM-5 tobacco use disorder and subjective sleep disturbances were maintained in multivariable analyses following adjustment for a range of health, lifestyle, and psychiatric factors (adjusted OR 1.11, 95%CI 1.00-1.23 and adjusted OR = 1.24, 95%CI 1.15-1.34, respectively); however, these relationships were fully explained by diagnoses of DSM-5 alcohol use disorder. CONCLUSIONS: Data from this large, representative survey indicate that the association between DSM-5 Tobacco use disorder and sleep disturbance is explained by underlying diagnoses of DSM-5 alcohol use disorder. Multifaceted substance abuse treatment protocols may improve treatment outcomes for affected patient groups.

Social and emotional loneliness and self-reported difficulty initiating and maintaining sleep (DIMS) in a sample of Norwegian university students.

Social and emotional loneliness negatively impact several areas of health, including sleep. However, few comprehensive population-based studies have evaluated this relationship. Over 12,000 students aged 21-35 years who participated in the student survey for higher education in Norway (the SHoT study) were assessed. Loneliness was assessed using the Social and Emotional Loneliness Scale. Difficulty initiating and maintaining sleep (DIMS) was assessed by a single-item subjective response on the depression scale of the Hopkins Symptoms Checklist (HSCL-25). Social loneliness was associated with more serious DIMS (unadjusted proportional odds-ratio [OR] = 2.69, 95% CI = 2.46-2.95). This association was attenuated following adjustment for anxiety (adjusted OR = 1.92, 95% CI = 1.75-2.10) and depression (adjusted OR = 1.48, 95% CI = 1.34-1.63), however was not substantially altered when all demographics and psychological distress were accounted for (fully adjusted OR = 1.46, 95% CI = 1.30-1.63). Emotional loneliness was also associated with more serious DIMS (unadjusted proportional OR = 2.33, 95% CI = 2.12-2.57). Adjustment for anxiety (adjusted OR = 1.96, 95% CI = 1.78-2.15) and depression (adjusted OR = 1.64, 95% CI = 1.48-1.80) attenuated, but did not extinguish this relationship in the fully adjusted model (adjusted OR = 1.22, 95% CI = 1.09-1.31). Mediation analyses revealed that the social loneliness-DIMS association was fully attributed to psychological distress, while the emotional loneliness-DIMS association was only partially mediated, and a direct association was still observed. Associations between social and emotional loneliness and subjective DIMS were embedded in a larger pattern of psychological distress. Mitigating underlying feelings of loneliness may reduce potentially deleterious effects on sleep health and psychological wellbeing in young adults.

Relationships Among Cognitive Function and Cerebral Blood Flow, Oxidative Stress, and Inflammation in Older Heart Failure Patients.

BACKGROUND: The mechanisms for cognitive impairment in heart failure (HF) are unclear. We investigated the relative contributions of cerebral blood flow velocity (BFV), oxidative stress, and inflammation to HF-associated cognitive impairment. METHODS AND RESULTS: Thirty-six HF patients (≥60 years) and 40 healthy controls (68 ± 7 vs 67 ± 5 years, P > .05; 69% vs 50% male, P > .05) completed the Cognitive Drug Research computerized assessment battery and Stroop tasks. Common carotid (CCA) and middle cerebral arterial BFV were obtained by transcranial Doppler. Blood samples were collected for oxidant (diacron-reactive oxygen metabolites; F2-isoprostanes), antioxidant (coenzyme Q10; CoQ10), and inflammatory markers (high-sensitivity C-reactive protein). Compared with controls, patients exhibited impaired attention (Cognitive Drug Research's Power of Attention domain, congruent Stroop) and executive function (incongruent Stroop). Multiple regression modeling showed that CCA-BFV and CoQ10 but not group predicted performance on attention and executive function. Additionally, in HF patients, CCA-BFV and CoQ10 (ß = -0.34 vs ß = -0.35) were significant predictors of attention, and CCA-BFV (ß = -0.34) was a predictor of executive function. CONCLUSIONS: Power of Attention and executive function is impaired in older HF patients, and reduced CCA-BFV and CoQ10 are associated with worse cognition. Interventions addressing these mechanisms may improve cognition in older HF patients.

The effect of Sailuotong (SLT) on neurocognitive and cardiovascular function in healthy adults: a randomised, double-blind, placebo controlled crossover pilot trial.

BACKGROUND: Sailuotong (SLT) is a standardised herbal medicine formula consisting of Panax ginseng, Ginkgo biloba, and Crocus sativus, and has been designed to enhance cognitive and cardiovascular function. METHODS: Using a randomised, double-blind, placebo controlled crossover design, this pilot study assessed the effect of treatment for 1 week with SLT and placebo (1 week washout period) on neurocognitive and cardiovascular function in healthy adults. Sixteen adults completed a computerised neuropsychological test battery (Compass), and had their electroencephalographic (EEG) activity and cardiovascular system function assessed. Primary outcome measures were cognitive test scores and oddball task event-related potential (ERP) component amplitudes. Secondary outcome measures were resting EEG spectral band amplitudes, and cardiovascular parameters. RESULTS: Treatment with SLT, compared to placebo, resulted in small improvements in working memory, a slight increase in auditory target (cf. nontarget) P3a amplitude, and a decrease in auditory N1 target (cf. nontarget) amplitude. There was no effect of SLT on EEG amplitude in delta, theta, alpha, or beta bands in both eyes open and eyes closed resting conditions, or on aortic and peripheral pulse pressure, and resting heartrate. CONCLUSIONS: Findings suggest that SLT has the potential to improve working memory performance in healthy adults; a larger sample size is needed to confirm this. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry Trial Registration Id: ACTRN12610000947000 .

The effects of long-chain omega-3 fish oils and multivitamins on cognitive and cardiovascular function: a randomized, controlled clinical trial.

OBJECTIVE: Fish oils and multivitamins are two of the most commonly used dietary supplements. Fish oil use may reduce vascular risk factors associated with cognitive decline, thus providing benefits to both heart and brain health. Multivitamins may also have direct effects on brain function. The present study investigated the effects of fish oil, with and without the addition of a multivitamin, on cognitive and cardiovascular function. METHODS: In a randomized, placebo-controlled, double-blind fashion, 160 healthy adults aged 50-70 years were randomized to receive either 3 g of fish oil (240 mg eicosapentaenoic acid [EPA] + 240 mg docosahexaenoic acid [DHA]) with a multivitamin, 6 g of fish oil (480 mg EPA + 480 mg DHA) with a multivitamin, or 6 g of fish oil without a multivitamin or a placebo. Cognitive performance, brachial blood pressure, and aortic (central) blood pressure were measured at baseline, 6 weeks, and 16 weeks. RESULTS: Treatment allocation had no effect on the primary cognitive outcomes at endpoint. Absolute increases in the red blood cell omega-3/6 ratio were associated with improvements in spatial working memory. The group receiving 6 g fish oil without the multivitamin displayed a significant decrease in aortic pulse pressure and aortic augmentation pressure, two measures of aortic blood pressure and aortic stiffness. CONCLUSIONS: Fish oil decreased aortic pulse pressure and augmentation pressure. Reductions in aortic blood pressure were not accompanied by consistent improvements in cognition.

MDMA, cortisol, and heightened stress in recreational ecstasy users.

Stress develops when an organism requires additional metabolic resources to cope with demanding situations. This review will debate how recreational 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can increase some aspects of acute and chronic stress in humans. Laboratory studies on the acute effects of MDMA on cortisol release and neurohormone levels in drug-free regular ecstasy/MDMA users have been reviewed, and the role of the hypothalamic-pituitary-adrenal (HPA) axis in chronic changes in anxiety, stress, and cognitive coping is debated. In the laboratory, acute ecstasy/MDMA use can increase cortisol levels by 100-200%, whereas ecstasy/MDMA-using dance clubbers experience an 800% increase in cortisol levels, because of the combined effects of the stimulant drug and dancing. Three-month hair samples of abstinent users revealed cortisol levels 400% higher than those in controls. Chronic users show heightened cortisol release in stressful environments and deficits in complex neurocognitive tasks. Event-related evoked response potential studies show altered patterns of brain activation, suggestive of increased mental effort, during basic information processing. Chronic mood deficits include more daily stress and higher depression in susceptible individuals. We conclude that ecstasy/MDMA increases cortisol levels acutely and subchronically and that changes in the HPA axis may explain why recreational ecstasy/MDMA users show various aspects of neuropsychobiological stress.

Effects of two doses of glucose and a caffeine-glucose combination on cognitive performance and mood during multi-tasking.

BACKGROUND: This study assessed the effects of two doses of glucose and a caffeine-glucose combination on mood and performance of an ecologically valid, computerised multi-tasking platform. MATERIALS AND METHODS: Following a double-blind, placebo-controlled, randomised, parallel-groups design, 150 healthy adults (mean age 34.78 years) consumed drinks containing placebo, 25 g glucose, 60 g glucose or 60 g glucose with 40 mg caffeine. They completed a multi-tasking framework at baseline and then 30 min following drink consumption with mood assessments immediately before and after the multi-tasking framework. Blood glucose and salivary caffeine were co-monitored. RESULTS: The caffeine-glucose group had significantly better total multi-tasking scores than the placebo or 60 g glucose groups and were significantly faster at mental arithmetic tasks than either glucose drink group. There were no significant treatment effects on mood. Caffeine and glucose levels confirmed compliance with overnight abstinence/fasting, respectively, and followed the predicted post-drink patterns. CONCLUSION: These data suggest that co-administration of glucose and caffeine allows greater allocation of attentional resources than placebo or glucose alone. At present, we cannot rule out the possibility that the effects are due to caffeine alone Future studies should aim at disentangling caffeine and glucose effects.

Reducing occupational stress with a B-vitamin focussed intervention: a randomized clinical trial: study protocol.

BACKGROUND: Workplace stress in Australia and other western countries has been steadily increasing over the past decade. It can be observed not only in terms of increased compensation claims but also costs due to absenteeism, loss of productivity at work and reduced psychological and physiological health and well-being. Given the cost and pervasive effects of stress in the modern workforce, time efficient and cost-effective interventions capable of reducing occupational stress (or strain) and burnout are urgently required for the improved well-being of stressed employees. One intervention gaining scientific traction is supplementation with nutritional interventions, particularly the B group vitamins. METHODS: This study was developed to examine the effects of B group vitamins on workplace stress and mood variables with a sample of full-time employed older adults who subjectively report feeling stressed. The study is a randomized, double-blind, placebo-controlled, parallel-groups clinical trial where 200 (N = 100/group) participants will be randomized to receive Blackmores® Executive B Stress Formula or placebo daily for a period of 6 months. Participants will be tested at baseline and 6 months post-randomization on workplace stress, cognitive, personality and mood measures, cardiovascular (brachial and aortic systolic and diastolic blood pressures as well as arterial stiffness), biochemical (assays to measure inflammation and safety) as well as genetic assessments (to assess stress processing) and neuroimaging measures (to investigate in vivo mechanisms of action of B vitamins). In addition to this pre- and post- supplementation testing, participants will also complete a battery of self-report questionnaires online to assess their stress and mood once a month for the duration of the study. The primary aim of the study is to investigate the effects of B vitamin supplementation on work related stress. The secondary aims are to explore the mechanisms underpinning any changes in mood or workplace stress due to the B vitamin intervention by examining relationships between cognitive, biological, neuroimaging and cardiovascular variables over 6 months. A subset of 40 participants (N = 20/group) will undergo neuroimaging at baseline and at 6 months using functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) in order to further explore in vivo mechanisms of action of B vitamins. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR):ACTRN12613000294752.