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Context Testosterone concentrations decline with age, and lower testosterone concentrations are associated with several morbidities, including sexual dysfunction, obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. Objective Because dietary habits play a critical role in weight regulation and T2DM management, the aim of this systematic review and meta-analysis was to summarize and critically evaluate the evidence from randomized controlled trials to determine the effects of calorie restriction (CR) on testosterone concentrations in men. Data Sources A literature search was conducted across 4 databases, from their inception until March 2020. Data Extraction The screening and data extraction were completed by 2 authors independently, and in a blinded manner, according to a priori inclusion and exclusion criteria. Data Analysis Of the 4198 studies identified from the initial search, 7 randomized controlled trials were included for data extraction. Significant increases in total testosterone concentrations were reported in 3 of 4 studies in which CR was examined with overweight or obese men, compared with the control groups. Significant decreases in total testosterone concentrations were reported in 2 of 3 studies in which the effects of CR were examined with normal-weight, healthy men, compared with the control groups. In all 4 studies that examined the effect of CR on sex hormone–binding globulin concentrations, the intervention significantly increased sex hormone–binding globulin concentrations compared with that of the control groups irrespective of body composition. Conclusion This systematic review and meta-analysis provide some evidence that CR affects testosterone concentrations in men and this effect depends on their body mass index. PROSPERO registration no. CRD42020173102

Objective/background To validate and extend on previous positive findings of the sleep-enhancing effects of saffron supplementation in adults with unsatisfactory sleep. Patients/methods In this 28-day, 3-arm, parallel-group, double-blind, randomised controlled trial, 120 adults with unsatisfactory sleep received either a placebo, 14 mg, or 28 mg of a standardised saffron extract (affron®), 1 h before bed. Outcome measures included the Pittsburgh Sleep Diary (with sleep quality ratings as the primary outcome measure), Insomnia Symptom Questionnaire (ISQ), Profile of Mood States, Restorative Sleep Questionnaire, the Functional Outcomes of Sleep Questionnaire, and evening salivary melatonin and cortisol concentrations. Results Compared to the placebo, saffron supplementation was associated with greater improvements in sleep quality ratings (primary outcome measure), mood ratings after awakening, the ISQ total score, and ISQ-insomnia classifications. However, there were no significant differences between the saffron and placebo groups in other questionnaire and sleep diary outcome measures. Sleep improvements were similar for the two administered saffron doses. Compared to the placebo, saffron supplementation was associated with increases in evening melatonin concentrations but did not affect evening cortisol. Saffron supplementation was well-tolerated with no reported significant adverse effects. Conclusions These results provide further validation of the sleep-enhancing effects of 28-days of saffron supplementation in adults with unsatisfactory sleep. Further research is required to examine the efficacy and safety of saffron supplementation using objective sleep measures, over a longer duration, in people presenting with a diagnosed insomnia disorder and other psychogenic and demographic characteristics, and into its potential sleep-enhancing mechanisms of action.

BackgroundThere is preliminary evidence to suggest curcumin can alleviate digestive symptoms in adults with self-reported digestive complaints and irritable bowel syndrome. However, in all these trials, curcumin was used as a component of a multi-herbal combination and there were consistent concerns associated with risk of bias in most studies. The goal of this study was to investigate the effects of a curcumin extract (Curcugen™) on gastrointestinal symptoms, mood, and overall quality of life in adults presenting with self-reported digestive complaints. Moreover, to determine the potential therapeutic mechanisms of action associated with curcumin, its effects on intestinal microbiota and small intestinal bowel overgrowth (SIBO) were examined.MethodsIn this 8-week, parallel-group, double-blind, randomised controlled trial, 79 adults with self-reported digestive complaints were recruited and randomised to receive either a placebo or 500 mg of the curcumin extract, Curcugen™. Outcome measures included the Gastrointestinal Symptom Rating Scale (GSRS), intestinal microbial profile (16S rRNA), Depression, Anxiety, and Stress Scale – 21 (DASS-21), Short Form-36 (SF-36), and SIBO breath test.ResultsBased on self-report data collected from 77 participants, curcumin was associated with a significantly greater reduction in the GSRS total score compared to the placebo. There was also a greater reduction in the DASS-21 anxiety score. No other significant between-group changes in self-report data were identified. An examination of changes in the intestinal microbial profile and SIBO test revealed curcumin had no significant effect on these parameters. Curcumin was well-tolerated with no significant adverse events.ConclusionsThe curcumin extract, Curcugen™, administered for 8 weeks at a dose of 500 mg once daily was associated with greater improvements in digestive complaints and anxiety levels in adults with self-reported digestive complaints. Compared to the placebo, there were no significant changes in intestinal microbiota or SIBO; however, further research using larger samples and testing methods that allow more detailed microbial analyses will be important. An investigation into other potential mechanisms associated with curcumin’s gastrointestinal-relieving effects will also be important such as examining its influence on the intestinal barrier function, inflammation, neurotransmitter activity, and visceral sensitivity.Trial registrationAustralian New Zealand Clinical Trials Registry, Trial ID.ACTRN12619001236189. Registered 6 September 2019.

Stress is the nonspecific response of the body to any demand for change. Excess or chronic psychological or environmental stress is associated with an increased risk of mental and physical diseases, with several mechanisms theorized to be associated with its detrimental effects. One underappreciated potential mechanism relates to the effects of psychological and environmental stress on micronutrient concentrations. Micronutrients (vitamins and minerals) are essential for optimal physical and mental function, with deficiencies associated with an array of diseases. In this article, animal and human studies investigating the effects of various psychological and environmental stressors on micronutrient concentrations are reviewed. In particular, the effects of psychological stress, sleep deprivation, and physical exercise on micronutrient concentrations and micronutrient excretion are summarized. Micronutrients identified in this review include magnesium, zinc, calcium, iron, and niacin. Overall, the bulk of evidence suggests stress can affect micronutrient concentrations, often leading to micronutrient depletion. However, before definitive conclusions about the effects of stress can be made, the impact of different stressors, stress severity, and acute versus chronic stress on micronutrient concentrations requires investigation. Moreover, the impact of stress on micronutrients in different populations varying in age, gender, and premorbid health status and the durability of changes after a stressor is resolved require examination. The medical, physical, and psychological implications of nutrient changes caused by a stressor also remain to be determined.

Context Saffron (Crocus sativus L.) has gained interest as a potential treatment in psychiatry. Objective This systematic review and meta-analysis sought to investigate the effect of saffron supplementation, as both an adjunctive therapy and monotherapy, on symptoms of depression and anxiety in clinical and general populations compared with pharmacotherapy or placebo. Data sources Using the PRISMA guidelines, a systematic literature review of randomized controlled trials was conducted. Data extraction A meta-analysis was conducted to determine treatment effect. Risk of bias was assessed using the Jadad scale. Results Twenty-three studies were included. Saffron had a large positive effect size when compared with placebo for depressive symptoms (g = 0.99, P < 0.001) and anxiety symptoms (g = 0.95, P < 0.006). Saffron also had a large positive effect size when used as an adjunct to antidepressants for depressive symptoms (g = 1.23, P = 0.028). Egger’s regression test found evidence of publication bias. Conclusions Saffron could be an effective intervention for symptoms of depression and anxiety; however, due to evidence of publication bias and lack of regional diversity, further trials are required. PROSPERO registration CRD42017070060.

Background The acute anxiolytic effects of the echinacea angustifolia extract (EP107TM) have been demonstrated in two previous human trials. The goals of this study were to examine the anxiolytic and mood-enhancing effects of echinacea angustifolia over a longer duration with a larger sample size. Methods In this 6-week, 3-arm, parallel-group, double-blind, randomised controlled trial, 108 adults with mild-to-moderately severe anxiety were recruited and randomised to receive either a placebo, 20 mg, or 40 mg of echinacea angustifolia, twice daily. Outcome measures included the Clinically Useful Anxiety Outcome Scale (CUXOS), Positive and Negative Affect Scale (PANAS), Short Form-36 (SF-36), and Bergen Insomnia Scale (BIS). Results Based on data collected from 104 participants, both doses of echinacea were associated with overall reductions in anxiety, although improvements were not different from the placebo. However, both doses of echinacea were associated with greater improvements in the PANAS positive and negative affect scores, and SF-36 emotional wellbeing score compared to the placebo. Limitations The positive improvements associated with echinacea were only identified via the secondary outcome measures and, therefore, require validation in future trials. Conclusions The echinacea angustifolia extract (EP107TM) administered for 6 weeks at a dose of 40 and 80 mg daily was not associated with greater improvements in anxiety in adults with mild-to-moderately severe anxiety compared to the placebo. However, there were greater improvements in positive and negative affect, and emotional wellbeing, suggesting antidepressant effects. Further studies using clearly-defined populations and validated outcome measures will be useful in future trials.

The aim of this study was to investigate the efficacy and suitability of a brief integrative intervention, Personalized Integrative Therapy (PI Therapy), for the treatment of adult depression and/or anxiety. In this 6-week, 3-arm, parallel-group, randomized trial, PI Therapy delivered alone or with nutritional supplements (PI Therapy + Supps) was compared to cognitive behavior therapy (CBT) in 48 adults with depression and/or anxiety. All treatments were delivered as a 1-day workshop plus 6 weeks of reminder phone text messages to reinforce topics and skills covered in the workshop. Affective symptoms decreased significantly and to the same extent in all 3 conditions. At the end of treatment, 33% to 58% of participants reported levels of depressive symptoms in the normal range, and 50% to 58% reported nonclinical levels of anxiety. Compared to CBT and PI Therapy, PI Therapy + Supps was associated with significantly greater improvements in sleep quality. These findings suggest that a brief integrative intervention with or without supplements was comparable to CBT in reducing affective symptoms in adults with depression and/or anxiety. However, sleep quality improved only in the PI Therapy + Supps condition. These findings will require replication with a larger cohort.

STUDY OBJECTIVES: Herbal medicines are frequently used by adults with sleep difficulties. However, evidence of their efficacy is limited. Therefore, the goal of this study was to examine the sleep-enhancing effects of a standardized saffron extract (affron). METHODS: This was a 28-day, parallel-group, double-blind, randomized controlled trial. Sixty-three healthy adults aged 18–70 with self-reported sleep problems were recruited and randomized to receive either saffron extract (affron; 14 mg twice daily) or a placebo. Outcome measures included the Insomnia Severity Index (ISI; primary outcome measure) collected at baseline and days 7, 14, 21, and 28 and the Restorative Sleep Questionnaire (RSQ) and the Pittsburgh Sleep Diary (PSD) collected on days −1, 0, 3, 7, 14, 27, and 28. RESULTS: Based on data collected from 55 participants, saffron was associated with greater improvements in ISI total score (P = .017), RSQ total score (P = .029), and PSD sleep quality ratings (P = .014) than the placebo. Saffron intake was well tolerated with no reported adverse effects. CONCLUSIONS: Saffron intake was associated with improvements in sleep quality in adults with self-reported sleep complaints. Further studies using larger samples sizes, treatment periods, objective outcome measures, and volunteers with varying demographic and psychographic characteristics are required to replicate and extend these findings. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Effects of Saffron on Sleep Quality in Healthy Adults with Self-Reported Unsatisfactory Sleep; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377781; Identifier: ACTRN12619000863134. CITATION: Lopresti AL, Smith SJ, Metse AP, Drummond PD. Effects of saffron on sleep quality in healthy adults with self-reported poor sleep: a randomized, double-blind, placebo-controlled trial. J Clin Sleep Med. 2020;16(6):937–947.

In this 28-day, randomised, double-blind, placebo-controlled trial, 100 adults with self-reported poor sleep received either a placebo or a standardised Bacopa monnieri extract (150 mg twice daily). Outcome measures included the Bergen Insomnia Scale (primary outcome measure), Functional Outcomes of Sleep Questionnaire, Pittsburgh Sleep Diary, Short Form-36 Health Survey, and the Depression, Anxiety, and Stress Scale. Changes in salivary concentrations of cortisol, dehydroepiandrosterone sulfate, immunoglobulin A (sIgA), α-amylase (sAA), C-reactive protein, melatonin, and the fatigue biomarker index were also assessed. Based on the Bergen Insomnia Scale, Bacopa monnieri did not improve sleep patterns more than the placebo; however, it was associated with greater improvements in emotional wellbeing, general health, and pain-related symptoms. Bacopa monnieri was also associated with greater reductions in sIgA and sAA compared to the placebo. Future clinical trials using varying doses, treatment periods, and objective outcome measures will be important to validate these findings.

Ashwagandha is a medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3000 years. Because interest and the popularity of ashwagandha has increased in several Western countries, there are an increasing number of human trials evaluating its efficacy across a range of conditions. Based on the PRISMA guidelines, human trials assessing the effects of ashwagandha on mental and/or physical conditions, and/or human performance, used as a stand-alone or adjunct intervention, and delivered as a single ingredient, were eligible for inclusion in this systematic review. Forty-one studies were identified examining the effects of ashwagandha on stress and anxiety, sexual function and fertility, athletic performance, cognitive performance, pain, fatigue, thyroid function, schizophrenia, diabetes, obsessive-compulsive disorder, insomnia, hypercholesterolemia, and tuberculosis. Results from most of these studies indicated positive effects from ashwagandha intake, although treatment dose, duration, and extract types varied significantly. Moreover, trials often comprised of small sample sizes and were primarily conducted in India (32 studies). Overall, the strongest evidence for therapeutic efficacy of ashwagandha is the alleviation of stress and anxiety symptoms. The results from this systematic review suggest ashwagandha has a potentially large array of therapeutic applications. However, while promising, the significant heterogeneity across studies and the limited number of investigations means further research utilising robust and adequately-powered study designs are required.

Objective:There is growing evidence confirming increased inflammation in a subset of adults with depression. The impact of this relationship has mostly been considered in biologically based interventions; however, it also has potential implications for psychological therapies. Cognitive behaviour therapy is the most commonly used psychological intervention for the treatment of depression with theories around its efficacy primarily based on psychological mechanisms. However, cognitive behaviour therapy may have an effect on, and its efficacy influenced by, physiological processes associated with depression. Accordingly, the purpose of this systematic review was to examine the relationship between cognitive behaviour therapy and inflammation.Method:Studies examining the anti-inflammatory effects of cognitive behaviour therapy in people with depression and other medical conditions (e.g. cancer, diabetes and heart disease) were examined. In addition, the relationship between change in inflammatory markers and change in depressive symptoms following cognitive behaviour therapy, and the influence of pre-treatment inflammation on cognitive behaviour therapy treatment response were reviewed.Results:A total of 23 studies investigating the anti-inflammatory effects of cognitive behaviour therapy were identified. In 14 of these studies, at least one reduction in an inflammatory marker was reported, increases were identified in three studies and no change was found in six studies. Three studies examined the relationship between change in inflammation and change in depressive symptoms following cognitive behaviour therapy. In two of these studies, change in depressive symptoms was associated with a change in at least one inflammatory marker. Finally, three studies examined the influence of pre-treatment inflammation on treatment outcome from cognitive behaviour therapy, and all indicated a poorer treatment response in people with higher premorbid inflammation.Conclusion:Preliminary evidence suggests inflammation should be considered within the context of cognitive behaviour therapy, although robust studies examining the relationship are sparse, and heterogeneity between studies and populations examined was high. The potential treatment implications of the bi-directional relationship between inflammation and cognitive behaviour therapy are discussed, and recommendations for future research are proposed.

Objectives There is preliminary evidence suggesting saffron may effectively treat menopausal symptoms. The aim of this study was to examine the tolerability and efficacy of a standardised saffron extract (affron®) on menopausal complaints in perimenopausal women. Methods In this 12-week, parallel-group, double-blind, randomised controlled trial, 86 perimenopausal women experiencing menopausal complaints received either a placebo or 14 mg of a saffron extract (affron®), twice daily. Outcome measures included the Greene Climacteric Scale (GCS), Positive and Negative Affect Schedule (PANAS), and Short Form-36 Health Survey (SF-36). Results Based on data collected from 82 participants, saffron was associated with greater improvements in mood and psychological symptoms compared to the placebo. Results from the GCS revealed a significantly greater reduction in the GCS psychological score (P = 0.032), characterised by a 33% reduction in anxiety and a 32% reduction in depression scores from baseline to week 12. There was also a significantly greater reduction in the PANAS negative affect score (P = 0.043) compared to the placebo. However, compared to the placebo, saffron was not associated with greater improvements in vasomotor symptoms, somatic symptoms, or other quality of life measures. Saffron intake was well tolerated with no reported major adverse events. Conclusions The saffron extract, affron®, administered for 12 weeks at a dose of 14 mg twice daily was associated with greater improvements in psychological symptoms. Further studies in perimenopausal women presenting with varying severity of menopausal symptoms, using different doses of saffron will be useful to examine in future clinical trials.

[Background]: Saffron has antidepressant and anxiolytic effects in adults with mild-to-moderate depression. However, this is the first study examining its mood-related effects in teenagers. [Methods]: In this 8-week, randomised, double-blind, placebo-controlled study, youth aged 12–16 years, with mild-to-moderate anxiety or depressive symptoms were given tablets containing placebo or a saffron extract (affron, 14 mg b.i.d). The youth and parent versions of the Revised Child Anxiety and Depression Scale (RCADS) were used as outcome measures. [Results]: 80 participants were enrolled and 68 completed the study. Based on youth self-reports, affron was associated with greater improvements in overall internalising symptoms (p = 0.049), separation anxiety (p = 0.003), social phobia (p = 0.023), and depression (p = 0.016). Total internalising scores decreased by an average of 33% compared to 17% in the placebo group (p = 0.029). However, parental reports of improvements were inconsistent as mean improvements in RCADS scores were greater in the saffron group (40% vs 26%) (p = 0.026), although no other significant differences were identified. affron was well-tolerated and there was a trend of reduced headaches in participants on the active treatment. [Limitations]: The use of a self-report instrument, limited study duration, single treatment dose, and non-clinical sample used in this study limit the generalisability of study findings. [Conclusion]: The administration of a standardised saffron extract (affron) for 8 weeks improved anxiety and depressive symptoms in youth with mild-to-moderate symptoms, at least from the perspective of the adolescent. However, these beneficial effects were inconsistently corroborated by parents., This study was funded by Pharmactive Biotech Products SL. The authors gratefully acknowledge Pharmactive Biotech Products SL Company for funding the project.

Ashwagandha ( Withania somnifera) is a herb commonly used in Ayurvedic medicine to promote youthful vigor, enhance muscle strength and endurance, and improve overall health. In this 16-week, randomized, double-blind, placebo-controlled, crossover study, its effects on fatigue, vigor, and steroid hormones in aging men were investigated. Overweight men aged 40–70 years, with mild fatigue, were given a placebo or an ashwagandha extract (Shoden beads, delivering 21 mg of withanolide glycosides a day) for 8 weeks. Outcome measures included the Profile of Mood States, Short Form (POMS-SF), Aging Males’ Symptoms (AMS) questionnaire, and salivary levels of DHEA-S, testosterone, cortisol, and estradiol. Fifty-seven participants were enrolled, with 50 people completing the first 8-week period of the trial and 43 completing all 16 weeks. Improvements in fatigue, vigor, and sexual and psychological well-being were reported over time, with no statistically significant between-group differences. Ashwagandha intake was associated with an 18% greater increase in DHEA-S ( p = .005) and 14.7% greater increase in testosterone ( p = .010) compared to the placebo. There were no significant between-group differences in cortisol and estradiol. In conclusion, the intake of a standardized ashwagandha extract (Shoden beads) for 8 weeks was associated with increased levels of DHEA-S and testosterone, although no significant between-group differences were found in cortisol, estradiol, fatigue, vigor, or sexual well-being. Further studies with larger sample sizes are required to substantiate the current findings.

Rates of obesity are higher than normal across a range of psychiatric disorders, including major depressive disorder, bipolar disorder, schizophrenia and anxiety disorders. While the problem of obesity is generally acknowledged in mental health research and treatment, an understanding of their bi-directional relationship is still developing. In this review the association between obesity and psychiatric disorders is summarised, with a specific emphasis on similarities in their disturbed biological pathways; namely neurotransmitter imbalances, hypothalamus-pituitary-adrenal axis disturbances, dysregulated inflammatory pathways, increased oxidative and nitrosative stress, mitochondrial disturbances, and neuroprogression. The applicability and effectiveness of weight-loss interventions in psychiatric populations are reviewed along with their potential efficacy in ameliorating disturbed biological pathways, particularly those mediating inflammation and oxidative stress. It is proposed that weight loss may not only be an effective intervention to enhance physical health but may also improve mental health outcomes and slow the rate of neuroprogressive disturbances in psychiatric disorders. Areas of future research to help expand our understanding of the relationship between obesity and psychiatric disorders are also outlined.

Background Curcumin, the principal curcuminoid derived from the spice turmeric, influences several biological mechanisms associated with major depression, namely those associated with monoaminergic activity, immune-inflammatory and oxidative and nitrosative stress pathways, hypothalamus-pituitary-adrenal (HPA) axis activity and neuroprogression. We hypothesised that curcumin would be effective for the treatment of depressive symptoms in individuals with major depressive disorder. Methods In a randomised, double-blind, placebo-controlled study, 56 individuals with major depressive disorder were treated with curcumin (500 mg twice daily) or placebo for 8 weeks. The primary measure was the Inventory of Depressive Symptomatology self-rated version (IDS-SR30). Secondary outcomes included IDS-SR30 factor scores and the Spielberger State-Trait Anxiety Inventory (STAI). Results From baseline to week 4, both curcumin and placebo were associated with improvements in IDS-SR30 total score and most secondary outcome measures. From weeks 4 to 8, curcumin was significantly more effective than placebo in improving several mood-related symptoms, demonstrated by a significant group x time interaction for IDS-SR30 total score (F1, 53=4.22, p=.045) and IDS-SR30 mood score (F1, 53=6.51, p=.014), and a non-significant trend for STAI trait score (F1, 48=2.86, p=.097). Greater efficacy from curcumin treatment was identified in a subgroup of individuals with atypical depression. Conclusions Partial support is provided for the antidepressant effects of curcumin in people with major depressive disorder, evidenced by benefits occurring 4 to 8 weeks after treatment. Limitations Investigations with larger sample sizes, over extended treatment periods, and with varying curcumin dosages are required.