An Examination into the Effects of a Nutraceutical Supplement on Cognition, Stress, Eye Health, and Skin Satisfaction in Adults with Self-Reported Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory (p = 0.037), but not for working memory (p = 0.418) or verbal learning (p = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire (p = 0.022), increased plasma brain-derived neurotrophic factor (p = 0.030), decreased plasma malondialdehyde (p = 0.040), and increased skin carotenoid concentrations (p = 0.006). However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.

Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Stress is a state of homeostasis in the body being challenged, resulting in a systemic response. It has become more prevalent in recent years and affects mental and physical health. AIMS: Evaluate the effects of ashwagandha on stress, fatigue, and sex hormones in overweight or mildly obese men and women with self-reported stress and fatigue. METHODS: Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial on overweight or mildly obese men and women aged 40-75 years, supplementing with 200 mg of an ashwagandha root extract (Witholytin®) twice daily. RESULTS/OUTCOMES: Supplementation with ashwagandha was associated with a significant reduction in stress levels based on the Perceived Stress Scale (primary outcome); however, the improvements were not significantly different to the placebo group (p = 0.867). Based on the Chalder Fatigue Scale, there was a statistically significant reduction in fatigue symptoms in the ashwagandha group compared to the placebo group (p = 0.016), and participants taking ashwagandha also experienced a significant increase in heart rate variability (p = 0.003). However, there were no significant between-group differences in other self-report outcome measures. In the men taking ashwagandha, there was a significant increase in the blood concentrations of free testosterone (p = 0.048) and luteinizing hormone (p = 0.002) compared to the placebo group. CONCLUSIONS/INTERPRETATION: The results of this study suggest that in overweight middle-to-older age adults experiencing high stress and fatigue, compared to the placebo, ashwagandha did not have a significantly greater impact on perceived stress levels. However, based on secondary outcome measures, it may have anti-fatigue effects. This may be via its impact on the autonomic nervous system. However, further research is required to expand on these current findings.

Examining the associations between testosterone and biomarkers as men age.

OBJECTIVES: Testosterone concentrations in men decline with advancing age. However, the cause of the decline is yet to be fully elucidated. Therefore, the aims of this study were to examine the associations between chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) with total testosterone (TT) and sex hormone-binding globulin (SHBG), using a large nationally-representative data set (National Health and Nutrition Examination Survey; NHANES). METHODS: NHANES is a cross-sectional survey, physical examination, and laboratory evaluation of a nationally-representative sample of a non-institutionalized United States population. Male participants aged ≥18 years during the NHANES 2013-2014 and NHANES 2015-2016 survey periods were selected for this analysis. The analysis included the following data: body mass index (BMI), oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA-IR), insulin, glucose, and age. RESULTS: An overweight or obese condition was significantly inversely associated with TT and SHBG, even after adjusting for other variables. Several variables associated with T2DM (OGTT, HOMA-IR, insulin, and glucose) were also inversely associated with TT; however, only the associations between OGTT and insulin with TT remained significant after adjusting for the other variables. Insulin and HOMA-IR levels were significantly inversely associated with SHBG; however, only the association between SHBG and pre-diabetic HOMA-IR levels remained significant after adjusting for the other variables. OGTT became significantly associated with SHBG after adjusting for the other variables. Age was significantly inversely associated with TT, but positively associated with SHBG, even after adjusting for other variables. CONCLUSION: The results of the present study, which is the largest to date, indicate that a marker of obesity, BMI, and some markers of T2DM are both independently and significantly inversely associated with TT and SHBG.

Effects of a polyphenol-rich grape and blueberry extract (Memophenol™) on cognitive function in older adults with mild cognitive impairment: A randomized, double-blind, placebo-controlled study.

Background: Polyphenols are naturally occurring organic compounds found in plants. Research suggests that their intake reduces the risk of cognitive decline and related dementias. Grapes and blueberries are polyphenol-rich foods that have attracted attention for their potential cognitive-enhancing effects. Purpose: Examine the effects of supplementation with a standardized and patented polyphenol-rich grape and blueberry extract (Memophenol™) on cognitive function in older adults with mild cognitive impairment. Study design: Two-arm, 6 month, parallel-group, randomized, double-blind, placebo-controlled trial. Methods: One hundred and forty-three volunteers aged 60 to 80 years with mild cognitive impairment were supplemented with either 150 mg of Memophenol™, twice daily or a placebo. Outcome measures included computer-based cognitive tasks, the Behavior Rating Inventory of Executive Function (BRIEF-A), the Cognitive Failures Questionnaire, and the CASP-19. Results: Compared to the placebo, Memophenol™ supplementation was associated with greater improvements in the speed of information processing (p = 0.020), visuospatial learning (p = 0.012), and the BRIEF-A global score (p = 0.046). However, there were no other statistically significant between-group differences in the performance of other assessed cognitive tests or self-report questionnaires. Memophenol™ supplementation was well-tolerated with no reports of significant adverse reactions. Conclusion: The promising results from this trial suggest that 6-months of supplementation with Memophenol™ may improve aspects of cognitive function in adults with mild cognitive impairment. Further research will be important to expand on the current findings and identify the potential mechanisms of action associated with the intake of this polyphenol-rich extract.

A randomized, double-blind, placebo-controlled trial investigating the effects of an Ocimum tenuiflorum (Holy Basil) extract (HolixerTM) on stress, mood, and sleep in adults experiencing stress.

Background: In Ayurveda, Ocimum tenuiflorum (Holy Basil) is referred to as "the elixir of life" and is believed to promote longevity and general wellbeing. Although limited, there are clinical trials to suggest Ocimum tenuiflorum has anti-stress effects. Purpose: Examine the effects of a standardized Ocimum tenuiflorum extract (HolixerTM) on subjective and objective measures of stress and sleep quality in adults experiencing stress. Study design: Two-arm, parallel-group, 8-week, randomized, double-blind, placebo-controlled trial. Australian and New Zealand Clinical Trials Registry trial registration number ACTRN12621000609853. Methods: One hundred volunteers aged 18-65 years received either 125 mg of Ocimum tenuiflorum twice daily or a placebo. Outcome measures included the Perceived Stress Scale (PSS) (primary outcome measure), Profile of Mood States, Athens Insomnia Scale (AIS), Restorative Sleep Questionnaire, and the Patient-Reported Outcomes Measurement Information System-29. Sleep quality was also assessed using a wrist-worn sleep tracker (Fitbit), and stress changes were examined by measuring between-group differences in hair cortisol and stress responses after exposure to an experiment stress procedure known as the Maastricht Acute Stress Test (MAST). Results: Compared to the placebo, Ocimum tenuiflorum supplementation was associated with greater improvements in PSS (p = 0.003) and AIS (p = 0.025) scores; and at week 8, concentrations in hair cortisol were also lower (p = 0.025). Moreover, Ocimum tenuiflorum supplementation was associated with a buffered stress responses after exposure to the MAST as demonstrated by significantly lower concentrations in salivary cortisol (p = 0.001), salivary amylase (p = 0.001), systolic (p = 0.010) and diastolic (p = 0.025) blood pressure, and subjective stress ratings (p < 0.001). Ocimum tenuiflorum supplementation was well-tolerated with no reports of major adverse effects. Conclusion: The results from this trial suggest that 8 weeks of supplementation with an Ocimum tenuiflorum extract (HolixerTM) may reduce objective and subjective measures of stress, and improve subjective measures of sleep quality. However, further research using gold-standard objective sleep measures will be required to substantiate the sleep-related findings. Clinical trial registration: https://www.anzctr.org.au/ACTRN12621000609853p.aspx, identifier: ACTRN12621000609853p.

An examination into the mental and physical effects of a saffron extract (affron®) in recreationally-active adults: A randomized, double-blind, placebo-controlled study.

Background: Saffron, derived from the stigmas of the Crocus Sativus flower, has been shown in several studies to improve mood and wellbeing in adults experiencing low mood and anxiety. The goals of this study were to examine its mental and physical effects in healthy, recreationally active adults. Methods: In this 6-week, randomized, double-blind, placebo-controlled study, 62 adults engaging in regular exercise were recruited and randomized to receive a placebo or 28 mg daily of a standardized saffron extract (affron®). Self-report outcome measures include the Physical Activity Enjoyment Scale, Profile of Mood States, and Patient-Reported Outcomes Measurement Information System-29. Participants also wore a wrist-worn heart rate, activity, and sleep monitoring device (WHOOP) to measure changes in sleep quality, resting heart rate, and heart rate variability. To help identify mechanisms of action associated with saffron intake, changes in plasma concentrations of brain-derived neurotrophic factor, oxytocin, and neuropeptide Y were also measured. Results: Based on data collected from all participants, there were no statistically significant between-group differences in changes in any of the outcome measures. However, when changes were analyzed by sex, there were statistically significant greater increases in enjoyment associated with exercise (p =.009) and heart rate variability (p =.001) in male participants taking saffron compared to the placebo. No statistically significant between-group differences were identified in females. Conclusions: The results of this trial suggest saffron may have beneficial effects in recreationally active males, as evidenced by increased exercise enjoyment and heart rate variability. However, no such benefits were identified in females. Future research using larger sample sizes, varying treatment periods, and additional outcome measures will be required to validate the results from this study and help clarify the mechanisms of action associated with saffron intake.This study was prospectively registered on 30 October 2020 with the Australian and New Zealand Clinical Trials Registry (Trial ID. ACTRN12621000501842).

The Effects of Lutein and Zeaxanthin Supplementation on Cognitive Function in Adults With Self-Reported Mild Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Lutein and zeaxanthin are fat-soluble, dietary carotenoids with high concentrations in human brain tissue. There have been a number studies confirming an association between lutein and zeaxanthin and cognitive function. PURPOSE: Examine the effects of lutein and zeaxanthin supplementation on cognitive function in adults with self-reported cognitive complaints. STUDY DESIGN: Two-arm, parallel-group, 6-month, randomized, double-blind, placebo-controlled trial. METHODS: Ninety volunteers aged 40-75 years received either 10 mg of lutein and 2 mg of zeaxanthin, once daily or a placebo. Outcome measures included computer-based cognitive tasks, the Cognitive Failures Questionnaire, Behavior Rating Inventory of Executive Function, Profile of Mood States, and the Patient-Reported Outcomes Measurement Information System-29. RESULTS: Compared to the placebo, lutein and zeaxanthin supplementation was associated with greater improvements in visual episodic memory (p = 0.005) and visual learning (p = 0.001). However, there were no other statistically-significant differences in performance on the other assessed cognitive tests or self-report questionnaires. Lutein and zeaxanthin supplementation was well-tolerated with no reports of significant adverse effects. CONCLUSION: The results from this trial suggest that 6-months of supplementation with lutein and zeaxanthin may improve visual memory and learning in community-dwelling adults with self-reported cognitive complaints. However, it had no other effect on other computer-based measures of cognitive performance or self-report measures of cognition, memory, mood, or physical function.

Potential Role of Curcumin for the Treatment of Major Depressive Disorder.

Curcumin is the major biologically active polyphenolic constituent in the turmeric plant (Curcuma longa) that has been shown to have antioxidant, anti-inflammatory, neuroprotective, anticancer, antimicrobial, and cardioprotective effects. Interest in curcumin as a treatment for mental health conditions has increased and there is an expanding body of preclinical and clinical research examining its antidepressant and anxiolytic effects. In this narrative review, human trials investigating the effects of curcumin for the treatment of depression or depressive symptoms are summarised. Using findings from in vitro, animal, and human trials, possible biological mechanisms associated with the antidepressant effects of curcumin are also explored. To increase the understanding of curcumin for the treatment of depression, directions for future research are proposed.

Examining the effects of calorie restriction on testosterone concentrations in men: a systematic review and meta-analysis.

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.

Modulation of the hypothalamic-pituitary-adrenal (HPA) axis by plants and phytonutrients: a systematic review of human trials.

INTRODUCTION: The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the stress response. Plants, herbs, spices, and plant-based nutrients may influence HPA-axis activity. OBJECTIVE: To evaluate randomised controlled, human trials assessing the effects of single plants or phytonutrients on HPA-axis related hormones. METHODS: A systematic review of PubMed, Cochrane library, and the Cumulative Index to Nursing and Allied Health Literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria comprised of human, randomised controlled studies with a control intervention examining the effects of a single herb, spice, plant, or extract on pre- and post-changes in blood, saliva, urine, or hair concentrations of cortisol, cortisone, corticotrophin-releasing hormone, or adrenocorticotropic hormone. Databases were searched from inception until October 2020. RESULTS: Fifty-two studies were identified examining the effects of ashwagandha, Korean ginseng, St John's Wort, cannabidiol, Rhodiola rosea, curcumin, cherry juice, asparagus, Jiaogulan, Black cohosh, Siberian ginseng, Bacopa monnieri, blueberries, green tea, Caralluma fimbriata, cashew apple juice, melon, American ginseng, Ginkgo biloba, grape juice, grapefruit juice, rosella, hops, mangosteen, holy basil, and pomegranate juice. Due to significant variability in study designs, the effect of phytonutrients on HPA-axis activity in humans was unclear. The most consistent finding was a morning, cortisol-lowering effect from ashwagandha supplementation. CONCLUSION: For most phytonutrients, the effects of supplementation on HPA-axis activity in humans is unclear. Before more definitive conclusions about the effects of phytonutrients on the HPA-axis can be made, further research is required.

Effects of an Oroxylum indicum Extract (Sabroxy®) on Cognitive Function in Adults With Self-reported Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Study.

Background: Oroxylum indicum has been used in traditional Ayurvedic medicine for the prevention and treatment of several diseases and may have neuroprotective effects. Purpose: Examine the effects of Oroxylum indicum on cognitive function in older adults with self-reported cognitive complaints. Study Design: Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial. Methods: Eighty-two volunteers received either 500 mg, twice daily of a standardized Oroxylum indicum extract or placebo. Outcome measures included several computer-based cognitive tasks, the Control, Autonomy, Self-Realization, and Pleasure scale (CASP-19), Cognitive Failures Questionnaire (CFQ), and the Montreal Cognitive Assessment (MoCA). Changes in the concentration of brain-derived neurotrophic factor (BDNF) were also examined. Results: Compared to the placebo, Oroxylum indicum was associated with greater improvements in episodic memory, and on several computer-based cognitive tasks such as immediate word recall and numeric working memory, and a faster rate of learning on the location learning task. However, there were no other significant differences in performance on the other assessed cognitive tests, the MoCA total score, or other self-report questionnaires. BDNF concentrations increased significantly in both groups, with no statistically-significant between-group differences. Oroxylum indicum was well tolerated except for an increased tendency for mild digestive complaints and headaches. Conclusion: The results of this first human trial on the cognitive-enhancing effects of Oroxylum indicum suggest that it is a promising herbal candidate for the improvement of cognitive function in older adults with self-reported cognitive complaints.

An investigation into an evening intake of a saffron extract (affron®) on sleep quality, cortisol, and melatonin concentrations in adults with poor sleep: a randomised, double-blind, placebo-controlled, multi-dose study.

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.

The Effects of a Saffron Extract (affron®) on Menopausal Symptoms in Women during Perimenopause: A Randomised, Double-Blind, Placebo-Controlled Study.

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.

An investigation into the anxiety-relieving and mood-enhancing effects of Echinacea angustifolia (EP107™): A randomised, double-blind, placebo-controlled study.

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.

Efficacy of a curcumin extract (Curcugen™) on gastrointestinal symptoms and intestinal microbiota in adults with self-reported digestive complaints: a randomised, double-blind, placebo-controlled study.

BACKGROUND: There 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. METHODS: In 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. RESULTS: Based 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. CONCLUSIONS: The 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 REGISTRATION: Australian New Zealand Clinical Trials Registry, Trial ID. ACTRN12619001236189 . Registered 6 September 2019.

An Investigation into the Effects of a Curcumin Extract (Curcugen®) on Osteoarthritis Pain of the Knee: A Randomised, Double-Blind, Placebo-Controlled Study.

Curcumin, a phytochemical from the spice turmeric, has anti-inflammatory properties and has been shown to have pain-relieving effects. In this 8-week, randomised, double-blind, placebo-controlled study, 101 adults with knee osteoarthritis received either 500 mg twice daily of a standardised curcumin extract (Curcugen®) or placebo. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score (KOOS), knee pain ratings, Japanese Orthopaedic Association Score for Osteoarthritic Knees (JOA), PROMIS-29, and performance-based testing comprising the 40-m fast-paced walk test, 6-min walk test, timed up-and-go test, and 30-s chair stand test. Compared to the placebo, curcumin significantly reduced the KOOS knee pain score (p = 0.009) and numeric knee pain ratings (p = 0.001). Curcumin was also associated with greater improvements (p ≤ 0.05) than the placebo on the timed up-and-go test, 6-min walk test, and the JOA total score; but not the 30-s chair stand test or 40-m fast-paced walk test. Pain-relieving medication was reduced in 37% of participants on curcumin compared to 13% on placebo. The findings support the potential efficacy of curcumin for the treatment of osteoarthritis of the knee but studies of longer duration, varying treatment doses, differing curcumin extracts, and the use of other objective outcome measures will be helpful to expand on these findings.

Examining the Effects of Herbs on Testosterone Concentrations in Men: A Systematic Review.

Testosterone concentrations in males tend to decline with advancing age. Low testosterone, also known as androgen deficiency (AD), is associated with an increased risk of morbidity and mortality. Currently, the primary treatment for AD is testosterone replacement therapy (TRT), which may exacerbate pre-existing medical conditions. Therefore, the use of alternative options, such as herbs, spices, plants, or their extracts, has been explored as a potential treatment option for AD. The aim of this systematic review was to summarize and critically evaluate randomized controlled trials published on the efficacy of single herbal ingredients on testosterone concentrations, in addition to its fractions or binding proteins, in men (≥18 y). From the 4 databases searched, there were 13 herbs identified in 32 studies, published between 2001 and 2019. The main findings of this review indicate that 2 herbal extracts, fenugreek seed extracts and ashwagandha root and root/leaf extracts, have positive effects on testosterone concentrations in men. Also, some evidence exists for another herb and herbal extract, Asian red ginseng and forskohlii root extract. Overall, 9 out of 32 studies demonstrated statistically significant increases in testosterone concentrations. Moreover, 6 studies out of 32 were judged as having a low risk of bias. Current evidence is largely based on young, nonclinical populations, with 16 out of 32 studies using men <40 y of age. Conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Also, further research is required before definitive conclusions on efficacy and safety can be made. This systematic review was registered at PROSPERO as CRD42020173623.

The Feasibility and Efficacy of a Brief Integrative Treatment for Adults With Depression and/or Anxiety: A Randomized Controlled Trial.

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.

Herbal treatments for migraine: A systematic review of randomised-controlled studies.

Herbal treatments are often used as a treatment for migraine. Therefore, an evaluation of their safety and efficacy is important. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and Cochrane Collaboration's tool for assessing the risk of bias, a systematic literature review of randomised, controlled human trials assessing the effects of herbal treatments delivered as a single ingredient for the acute or prophylactic treatment of migraine were conducted. Studies were identified through electronic database searches on Medline (Pubmed), Cochrane Library, Scopus, and CINAHL. Nineteen studies were identified examining the effects on migraine of feverfew, butterbur, curcumin, menthol/peppermint oil, coriander, citron, Damask rose, chamomile, and lavender. Overall, findings on the efficacy of feverfew were mixed and there was positive, albeit limited evidence for butterbur. There were positive, preliminary findings on curcumin, citron, and coriander as a prophylactic treatment for migraine, and the use of menthol and chamomile as an acute treatment. However, the risk of bias was high for many studies. The results of this systematic review suggest that several herbal medicines, via their multifactorial physiological influences, present as potential options to enhance the treatment of migraine. However, further high-quality research is essential to examine their efficacy and safety as a treatment for migraine.

Effects of saffron on sleep quality in healthy adults with self-reported poor sleep: a randomized, double-blind, placebo-controlled trial.

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.