A Combination of Green Tea, Rhodiola, Magnesium, and B Vitamins Increases Electroencephalogram Theta Activity During Attentional Task Performance Under Conditions of Induced Social Stress.

Background: A combination of green tea, rhodiola and magnesium with B vitamins has previously been reported to significantly increase EEG resting state theta, attenuate subjective stress, anxiety and mood disturbance, and heighten subjective and autonomic arousal under acute psychosocial laboratory stress. Here we examine the capacity of green tea and rhodiola extract administered in combination or in isolation with magnesium and B vitamins to moderate spectral brain activity during attentional task performance under stress. Materials and Methods: One-hundred moderately stressed adults received oral supplementation of (i) Mg + B vitamins + green tea + rhodiola; (ii) Mg + B vitamins + rhodiola; (iii) Mg + B vitamins + green tea; or (iv) placebo, in a double-blind, randomised, placebo-controlled, parallel-group design (Clinicaltrials.gov: NCT03262376; 25/0817). Participants completed an attention switching and emotionally threatening attentional bias task after stress induction (Trier Social Stress Test). Spectral alpha and theta brain activity and event related potentials (ERPs) were recorded during cognitive task performance by electroencephalogram (EEG; BioSemi ActiveTwo 64 channel). Results: The combined treatment of Mg + B vitamins + green tea + rhodiola significantly increased frontal midline theta vs. placebo and rhodiola in isolation during the attention switching task, specifically in anticipation of a change in task performance parameter. The combined treatment also significantly increased contralateral theta activation in relation to viewing emotionally threatening images in the left (vs. placebo and rhodiola in isolation) and right parietal (vs. placebo) regions. Further, this treatment demonstrated significantly heightened ipsilateral left parietal theta activation in relation to viewing emotionally threatening images. The combined treatment attenuated a decrease in alpha power during the attentional bias task evident in comparator treatments, but this did not reach significance. No significant effects of treatments on behavioural performance or ERP were found. Conclusion: The combination of Mg + B vitamins + green tea + rhodiola increased spectral theta brain activity during the execution of two attentional tasks suggestive of a potential to increase attentional capacity under conditions of stress. Further examination of these ingredients in relation to attentional performance under stress is warranted to ascertain if functional benefits suggested by theta activation can be shown behaviourally.

A combination of green tea, rhodiola, magnesium and B vitamins modulates brain activity and protects against the effects of induced social stress in healthy volunteers.

BACKGROUND: Magnesium (Mg), green tea and rhodiola extracts have, in isolation, been shown to possess stress and anxiety relieving effects. Green tea and rhodiola have been shown to modulate EEG oscillatory brain activity associated with relaxation and stress perception. The combined capacity of these ingredients to confer protective effects under conditions of acute stress has yet to be examined. We tested the hypothesis that a combination of Mg (with B vitamins) + green tea + rhodiola would acutely moderate the effects of stress exposure. METHODS: A double blind, randomised, placebo controlled, parallel group design was employed (Clinicaltrials.gov:NCT03262376; 25/0817). One hundred moderately stressed adults received oral supplementation of either (i) Mg + B vitamins + green tea + rhodiola; (ii) Mg + B vitamins + rhodiola; (iii) Mg + B vitamins + green tea; or (iv) placebo. After supplementation participants were exposed to the Trier Social Stress Test. The effects of the study treatments on electroencephalogram (EEG) resting state alpha and theta, subjective state/mood, blood pressure, heart rate variability and salivary cortisol responses after acute stress exposure were assessed. RESULTS: The combined treatment significantly increased EEG resting state theta (p < .02) - considered indicative of a relaxed, alert state, attenuated subjective stress, anxiety and mood disturbance, and heightened subjective and autonomic arousal (p < .05). CONCLUSIONS: Mg, B vitamins, rhodiola and green tea extracts are a promising combination of ingredients that may enhance coping capacity and offer protection from the negative effects of stress exposure.Trial registration: ClinicalTrials.gov identifier: NCT03262376.

Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial.

Magnesium status and vitamin B6 intake have been linked to mental health and/or quality of life (QoL). In an 8-week Phase IV randomised controlled study in individuals with low magnesemia and severe/extremely severe stress but who were otherwise healthy, greater stress reduction was achieved with magnesium combined with vitamin B6 than with magnesium alone. We present a previously unreported secondary analysis of the effect of magnesium, with and without vitamin B6, on depression, anxiety, and QoL. Adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 were randomised 1:1 to magnesium + vitamin B6 combination (Magne B6® ; daily dose 300 and 30 mg, respectively) or magnesium alone (Magnespasmyl® ; daily dose 300 mg). Outcomes included changes from baseline in DASS-42 depression and anxiety scores, and QoL (Short Form-36 Health Survey). DASS-42 anxiety and depression scores significantly improved from baseline to week 8 with both treatments, particularly during the first 4 weeks. Improvement in QoL continued over 8 weeks. Participants' perceived capacity for physical activity in daily life showed greater improvement with magnesium + vitamin B6 than magnesium alone (Week 4). In conclusion, magnesium supplementation, with or without vitamin B6, could provide a meaningful clinical benefit in daily life for individuals with stress and low magnesemia.

Is Magnesium Supplementation an Effective Nutritional Method to Reduce Stress in Domestic Pigs? A Systematic Review.

In commercial pig production, stressful events are common and can have detrimental impacts on the pig's health and welfare, as well as on the performance of the farm. Supplementary magnesium may reduce stress, and subsequent harmful and aggressive behaviors, that occur during stressful events, such as regrouping. However, reports on the efficacy of this treatment are mixed. We aimed to systematically review the studies in which magnesium was given to pigs to examine the effects on measures of stress. Of the 16 studies included in the final corpus, 10 reported at least one statistically significant beneficial effect of supplementary magnesium on reducing stress. However, two studies found that magnesium significantly increased stress suggesting supplementary dietary magnesium may be harmful in some cases. Overall, there are a limited number of studies investigating the possible effect of magnesium on reducing stress in pigs, and although results were varied, the majority found beneficial effects of supplementary magnesium.

Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial.

INTRODUCTION: Animal and clinical studies suggest complementary effects of magnesium and high-dose pyridoxine (vitamin B6) on stress reduction. This is the first randomized trial evaluating the effects of combined magnesium and vitamin B6 supplementation on stress in a stressed population with low magnesemia using a validated measure of perceived stress. METHODS: In this Phase IV, investigator-blinded trial (EudraCT: 2015-003749-24), healthy adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 and serum magnesium concentration 0.45 mmol/L-0.85 mmol/L, were randomized 1:1 to magnesium-vitamin B6 combination (Magne B6 [Mg-vitamin B6]; daily dose 300 mg and 30 mg, respectively) or magnesium alone (Magnespasmyl [Mg]; daily dose 300 mg). Outcomes included change in DASS-42 stress subscale score from baseline to Week 8 (primary endpoint) and Week 4, and incidence of adverse events (AEs). RESULTS: In the modified intention-to-treat analysis (N = 264 subjects), both treatment arms substantially reduced DASS-42 stress subscale score from baseline to Week 8 (Mg-vitamin B6, 44.9%; Mg 42.4%); no statistical difference between arms was observed (p>0.05). An interaction (p = 0.0097) between baseline stress level and treatment warranted subgroup analysis (as per statistical plan); adults with severe/extremely severe stress (DASS-42 stress subscale score ≥25; N = 162) had a 24% greater improvement with Mg-vitamin B6 versus Mg at Week 8 (3.16 points, 95% CI 0.50 to 5.82, p = 0.0203). Consistent results were observed in the per protocol analysis and at Week 4. Overall, 12.1% of Mg-vitamin B6 treated and 17.4% of Mg-treated subjects experienced AEs potentially treatment related. CONCLUSIONS: These findings suggest oral Mg supplementation alleviated stress in healthy adults with low magnesemia and the addition of vitamin B6 to Mg was not superior to Mg supplementation alone. With regard to subjects with severe/extremely severe stress, this study provides clinical support for greater benefit of Mg combined with vitamin B6.

A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota.

OBJECTIVE: Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). DESIGN: A randomised, open-label, cross-over trial of 8 weeks' treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week 'washout' period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. RESULTS: Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or ß diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. CONCLUSION: Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. TRIAL REGISTRATION NUMBER: ISRCTN18662143.

Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England.

OBJECTIVE: Severe vitamin D deficiency is a recognised cause of skeletal muscle fatigue and myopathy. The aim of this study was to examine whether chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with altered circulating vitamin D metabolites. DESIGN: Cohort study. SETTING: UK university hospital, recruiting from April 2014 to April 2015. PARTICIPANTS: Ninety-two patients with CFS/ME and 94 age-matched healthy controls (HCs). MAIN OUTCOME MEASURES: The presence of a significant association between CFS/ME, fatigue and vitamin D measures. RESULTS: No evidence of a deficiency in serum total 25(OH) vitamin D (25(OH)D2 and 25(OH)D3 metabolites) was evident in individuals with CFS/ME. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis revealed that total 25(OH)D was significantly higher (p=0.001) in serum of patients with CFS/ME compared with HCs (60.2 and 47.3 nmol/L, respectively). Analysis of food/supplement diaries with WinDiets revealed that the higher total 25(OH) vitamin D concentrations observed in the CFS/ME group were associated with increased vitamin D intake through use of supplements compared with the control group. Analysis of Chalder Fatigue Questionnaire data revealed no association between perceived fatigue and vitamin D levels. CONCLUSIONS: Low serum concentrations of total 25(OH)D do not appear to be a contributing factor to the level of fatigue of CFS/ME.

The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review.

BACKGROUND: Anxiety related conditions are the most common affective disorders present in the general population with a lifetime prevalence of over 15%. Magnesium (Mg) status is associated with subjective anxiety, leading to the proposition that Mg supplementation may attenuate anxiety symptoms. This systematic review examines the available evidence for the efficacy of Mg supplementation in the alleviation of subjective measures of anxiety and stress. METHODS: A systematic search of interventions with Mg alone or in combination (up to 5 additional ingredients) was performed in May 2016. Ovid Medline, PsychInfo, Embase, CINAHL and Cochrane databases were searched using equivalent search terms. A grey literature review of relevant sources was also undertaken. RESULTS: 18 studies were included in the review. All reviewed studies recruited samples based upon an existing vulnerability to anxiety: mildly anxious, premenstrual syndrome (PMS), postpartum status, and hypertension. Four/eight studies in anxious samples, four/seven studies in PMS samples, and one/two studies in hypertensive samples reported positive effects of Mg on subjective anxiety outcomes. Mg had no effect on postpartum anxiety. No study administered a validated measure of subjective stress as an outcome. CONCLUSIONS: Existing evidence is suggestive of a beneficial effect of Mg on subjective anxiety in anxiety vulnerable samples. However, the quality of the existing evidence is poor. Well-designed randomised controlled trials are required to further confirm the efficacy of Mg supplementation.

The effects of magnesium supplementation on subjective anxiety.

Experimental studies of anxiety in animal models, and evidence of efficacious outcomes of magnesium (Mg) supplementation in the treatment of acute clinical affective disorders, has increased interest in Mg as a potential novel treatment for symptoms of mild/moderate subjective anxiety. This short review examines the existing evidence for the effects of Mg supplementation on subjective anxiety in humans. Additionally, evidence from three unpublished studies that examined Mg and vitamin B6 intake on subjective anxiety is summarised to supplement the existing literature. CONCLUSIONS: The efficacy of Mg in the treatment of anxiety in the mildly anxious and those reporting premenstrual syndrome-related anxiety is suggestive of a beneficial effect of Mg intake. Further randomised controlled trials are warranted to further establish the efficacy of Mg as a novel treatment for subjective anxiety.

Assessment of the quality and content of website health information about herbal remedies for menopausal symptoms.

OBJECTIVE: To assess the quality, readability and coverage of website information about herbal remedies for menopausal symptoms. STUDY DESIGN: A purposive sample of commercial and non-commercial websites was assessed for quality (DISCERN), readability (SMOG) and information coverage. MAIN OUTCOME MEASURES: Non-parametric and parametric tests were used to explain the variability of these factors across types of websites and to assess associations between website quality and information coverage. RESULTS: 39 sites were assessed. Median quality and information coverage scores were 44/80 and 11/30 respectively. The median readability score was 18.7, similar to UK broadsheets. Commercial websites scored significantly lower on quality (p=0.014), but there were no statistical differences for information coverage or readability. There was a significant positive correlation between information quality and coverage scores irrespective of website provider (r=0.69, p<0.001, n=39). CONCLUSION: Overall website quality and information coverage are poor and the required reading level high.

Concord grape juice, cognitive function, and driving performance: a 12-wk, placebo-controlled, randomized crossover trial in mothers of preteen children.

BACKGROUND: Daily consumption of Concord grape juice (CGJ) over 3-4 mo has been shown to improve memory function in adults with mild cognitive impairment and reduce blood pressure in hypertensive adults. These benefits likely result from the high concentration of polyphenols in CGJ. Increased stress can impair cognitive function and elevate blood pressure. Thus, we examined the potential beneficial effect of CGJ in individuals with somewhat stressful and demanding lifestyles. OBJECTIVE: We sought to examine the effects of the daily consumption of CGJ for 12 wk on cognitive function, driving performance, and blood pressure in healthy, middle-aged working mothers. DESIGN: Twenty-five healthy mothers (aged 40-50 y) of preteen children who were employed for ≥30 h/wk consumed 12 ounces (355 mL) of either CGJ (containing 777 mg total polyphenols) or an energy-, taste-, and appearance-matched placebo daily for 12 wk according to a randomized crossover design with a 4-wk washout. Verbal and spatial memory, executive function, attention, blood pressure, and mood were assessed at baseline and at 6 and 12 wk. Immediately after the cognitive battery, a subsample of 17 women completed a driving performance assessment at the University of Leeds Driving Simulator. The 25-min driving task required participants to match the speed and direction of a lead vehicle. RESULTS: Significant improvements in immediate spatial memory and driving performance were observed after CGJ relative to placebo. There was evidence of an enduring effect of CGJ such that participants who received CGJ in arm 1 maintained better performance in the placebo arm. CONCLUSIONS: Cognitive benefits associated with the long-term consumption of flavonoid-rich grape juice are not exclusive to adults with mild cognitive impairment. Moreover, these cognitive benefits are apparent in complex everyday tasks such as driving. Effects may persist beyond the cessation of flavonoid consumption, and future studies should carefully consider the length of washout within crossover designs. This trial was registered at clinicaltrials.gov as NCT01411631.

Dietary intake of 20 polyphenol subclasses in a cohort of UK women.

BACKGROUND: Establishing and linking the proposed health benefits of dietary polyphenols to their consumption requires measurement of polyphenol intake in appropriate samples and an understanding of factors that influence their intake in the general population. METHODS: This study examined polyphenol intake estimated from 3- and 7-day food diaries in a sample of 246 UK women aged 18-50 years. Estimation of the intake of 20 polyphenol subclasses commonly present in foods consumed by the sample studied was done using Phenol-Explorer(®) and USDA polyphenol databases. Women were participants in the Leeds Women's Wellbeing Study (LWW) (n = 143), a dietary intervention study aimed at overweight women (mean age 37.2 ± 9.4 years; mean BMI 30.8 ± 3.1 kg/m(2)), and the Diet and Health Study (DH) (n = 103) which aimed to examine the relationship between polyphenol intake and cognitive function (mean age 25.0 ± 9.0 years; mean BMI 24.5 ± 4.6 kg/m(2)). RESULTS: The estimated intake of polyphenol subclasses was significantly different between the two samples (p < 0.01) with consumption of 1292 ± 844 and 808 ± 680 mg/day for the LWW and DH groups, respectively. Flavanols and hydroxycinnamic acids were the most important contributors to the polyphenols consumed by both groups, owing to tea and coffee consumption. Other major polyphenol food sources included fruits, vegetables and processed foods. CONCLUSION: Older women consumed more polyphenol-containing foods and beverages, which was due to the higher coffee and tea consumption amongst the LWW participants.

The efficacy of Hypericum perforatum (St John's wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Premenstrual syndrome (PMS) is a common condition. Some of the most widely prescribed medications are selective serotonin reuptake inhibitors (SSRIs), based on the hypothesized role of serotonin in the production of PMS symptoms. PMS sufferers, especially those experiencing mild to moderate symptoms, are often reluctant to take this form of medication and instead buy over-the-counter preparations to treat their symptoms, for which the evidence base with regard to efficacy is limited. Hypericum perforatum (St John's wort) influences the serotonergic system. As such, this widely available herbal remedy deserves attention as a PMS treatment. OBJECTIVE: To investigate the effectiveness of Hypericum perforatum on symptoms of PMS. STUDY DESIGN: This randomized, double-blind, placebo-controlled, crossover study was conducted between November 2005 and June 2007. SETTING: Institute of Psychological Sciences, University of Leeds, Leeds, UK. PARTICIPATION: 36 women aged 18-45 years with regular menstrual cycles (25-35 days), who were prospectively diagnosed with mild PMS. INTERVENTION: Women who remained eligible after three screening cycles (n = 36) underwent a two-cycle placebo run-in phase. They were then randomly assigned to receive Hypericum perforatum tablets 900 mg/day (standardized to 0.18% hypericin; 3.38% hyperforin) or identical placebo tablets for two menstrual cycles. After a placebo-treated washout cycle, the women crossed over to receive placebo or Hypericum perforatum for two additional cycles. MAIN OUTCOME MEASURES: Symptoms were rated daily throughout the trial using the Daily Symptom Report. Secondary outcome measures were the State Anxiety Inventory, Beck Depression Inventory, Aggression Questionnaire and Barratt Impulsiveness Scale. Plasma hormone (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol, progesterone, prolactin and testosterone) and cytokine (interleukin [IL]-1beta, IL-6, IL-8, interferon [IFN]-gamma and tumour necrosis factor [TNF]-alpha) levels were measured in the follicular and luteal phases during Hypericum perforatum and placebo treatment. RESULTS: Hypericum perforatum was statistically superior to placebo in improving physical and behavioural symptoms of PMS (p < 0.05). There were no significant effects of Hypericum perforatum compared with placebo treatment for mood- and pain-related PMS symptoms (p > 0.05). Plasma hormone (FSH, LH, estradiol, progesterone, prolactin and testosterone) and cytokine (IL-1beta, IL-6, IL-8, IFNgamma and TNFalpha) levels, and weekly reports of anxiety, depression, aggression and impulsivity, also did not differ significantly during the Hypericum perforatum and placebo cycles (p > 0.05). CONCLUSION: Daily treatment with Hypericum perforatum was more effective than placebo treatment for the most common physical and behavioural symptoms associated with PMS. As proinflammatory cytokine levels did not differ significantly between Hypericum perforatum and placebo treatment, these beneficial effects are unlikely to be produced through this mechanism of action alone. Further work is needed to determine whether pain- and mood-related PMS symptoms benefit from longer treatment duration. Trial registration number (International Standard Randomised Controlled Trial Number Register) ISRCTN31487459.

The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis.

BACKGROUND: In observational studies anaemia and iron deficiency are associated with cognitive deficits, suggesting that iron supplementation may improve cognitive function. However, due to the potential for confounding by socio-economic status in observational studies, this needs to be verified in data from randomised controlled trials (RCTs). AIM: To assess whether iron supplementation improved cognitive domains: concentration, intelligence, memory, psychomotor skills and scholastic achievement. METHODOLOGY: Searches included MEDLINE, EMBASE, PsychINFO, Cochrane CENTRAL and bibliographies (to November 2008). Inclusion, data extraction and validity assessment were duplicated, and the meta-analysis used the standardised mean difference (SMD). Subgrouping, sensitivity analysis, assessment of publication bias and heterogeneity were employed. RESULTS: Fourteen RCTs of children aged 6+, adolescents and women were included; no RCTs in men or older people were found. Iron supplementation improved attention and concentration irrespective of baseline iron status (SMD 0.59, 95% CI 0.29 to 0.90) without heterogeneity. In anaemic groups supplementation improved intelligence quotient (IQ) by 2.5 points (95% CI 1.24 to 3.76), but had no effect on non-anaemic participants, or on memory, psychomotor skills or scholastic achievement. However, the funnel plot suggested modest publication bias. The limited number of included studies were generally small, short and methodologically weak. CONCLUSIONS: There was some evidence that iron supplementation improved attention, concentration and IQ, but this requires confirmation with well-powered, blinded, independently funded RCTs of at least one year's duration in different age groups including children, adolescents, adults and older people, and across all levels of baseline iron status.

Zinc supplementation at conventional doses does not improve the disturbance of taste perception in hemodialysis patients.

OBJECTIVE: To determine the effect of zinc supplementation on taste perception in a group of hemodialysis patients. DESIGN AND SETTING: Double-blind randomized placebo-controlled study in a teaching hospital dialysis unit. PATIENTS: Fifteen stable hemodialysis patients randomized to placebo (6 male, 2 female; median age, 67; range, 30 to 72 years) or treatment (5 male, 2 female; median age, 60; range, 31 to 76 years). INTERVENTION: Treatment group received zinc sulfate 220 mg per day for 6 weeks, and the placebo group received an apparently identical dummy pill. MAIN OUTCOME MEASURES: Taste scores by visual analogue scales, normalized protein catabolic rate and plasma, whole blood and red cell zinc levels. RESULTS: At baseline, sweet and salt tastes were identified correctly by both groups. Sour was often confused with salt. Sour solutions of different concentrations were not distinguishable. Taste scores were not different after 6 weeks for either group. There was no significant increment in zinc levels or normalized protein catabolic rate for either group. CONCLUSION: We found a disturbance of taste perception in hemodialysis patients, particularly for the sour modality, which was not corrected by this regimen of zinc supplementation. These results cast doubts on the conclusions of earlier studies that indicated an improvement in taste after zinc supplementation.