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

Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study

Background Several studies have supported the antidepressant effects of curcumin (from the spice turmeric) and saffron for people with major depressive disorder. However, these studies have been hampered by poor designs, small sample sizes, short treatment duration, and similar intervention dosages. Furthermore, the antidepressant effects of combined curcumin and saffron administration are unknown. Methods In a randomised, double-blind, placebo-controlled study, 123 individuals with major depressive disorder were allocated to one of four treatment conditions, comprising placebo, low-dose curcumin extract (250 mg b.i.d.), high-dose curcumin extract (500 mg b.i.d.), or combined low-dose curcumin extract plus saffron (15 mg b.i.d.) for 12 weeks. The outcome measures were the Inventory of Depressive Symptomatology self-rated version (IDS-SR30) and Spielberger State-Trait Anxiety Inventory (STAI). Results The active drug treatments (combined) were associated with significantly greater improvements in depressive symptoms compared to placebo (p=.031), and superior improvements in STAI-state (p<.001) and STAI-trait scores (p=.001). Active drug treatments also had greater efficacy in people with atypical depression compared to the remainder of patients (response rates of 65% versus 35% respectively, p=.012). No differences were found between the differing doses of curcumin or the curcumin/saffron combination. Limitations Investigations with larger sample sizes are required to examine the efficacy of differing doses of curcumin and saffron/curcumin combination. Its effects in people with atypical depression also require examination in larger scale studies. Conclusions Active drug treatments comprising differing doses of curcumin and combined curcumin/saffron were effective in reducing depressive and anxiolytic symptoms in people with major depressive disorder

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

A review of nutrient treatments for paediatric depression

Paediatric depression is estimated to affect 15–20% of youths prior to adulthood and is associated with significant social, educational and physical impairment. Current treatments comprise moderately efficacious psychological therapies and pharmaceutical antidepressants. However, nutritional therapies are also available and are regularly sought by people with depressive illnesses and parents of depressed youths. In this narrative review, studies examining the antidepressant effects of individual nutritional supplements in child and adolescent populations are appraised. Epidemiological studies examining the relationship between nutritional status and paediatric depression, or depressive symptoms are also reviewed. Nutrients covered in this article include: omega-3 polyunsaturated fatty acids, s-adenosylmethionine, vitamin C, vitamin D, zinc, iron and B-vitamins. Although several of these nutrients present as promising treatments for paediatric depression, there is a lack of high-quality studies examining the antidepressant effects of all the aforementioned ingredients. Before nutritional treatments are accepted as validated treatments for paediatric depression, further high-quality studies are required

Oxidative and nitrosative stress in ADHD: Possible causes and the potential of antioxidant-targeted therapies

Attention deficit hyperactivity disorder (ADHD) has a complex aetiology although theories associated with disturbances in dopaminergic and noradrenergic activity are most commonly cited. The importance of these catecholamines in ADHD is supported by its effective treatment utilising stimulant and non-stimulant medications that modify their activity. Recently, there has been interest in oxidative and nitrosative stress (O&NS) in ADHD and its potential to contribute to this condition. In this article, research investigating O&NS in ADHD is reviewed and its impact on catecholaminergic activity and neurological structure is discussed. Lifestyle, environmental, psychological and nutritional influences on O&NS in people with ADHD are reviewed, and evidence for the therapeutic efficacy of antioxidant-related therapies is assessed. A selection of interventions with antioxidant mechanisms is presented as potential options for the treatment of ADHD. However, further research is required to help elucidate the role of O&NS and antioxidants for the prevention and management of ADHD

Dysregulated biological pathways in major depression: An examination of the antidepressant effects of curcumin

Major depression is associated with multiple dysregulated biological pathways which are influenced by an array of lifestyle, psychological, environmental and biological factors. Nutraceuticals including curcumin, derived from the Indian spice turmeric, also have the potential to influence these depressogenic pathways. Consequently, the aims of this thesis were to: 1. Review and integrate research on dysregulated biological pathways, namely those associated with neurotransmitter imbalances, immuno-inflammatory processes, hypothalamus-pituitary-adrenal axis dysregulation, oxidative and nitrosative stress, mitochondrial dysfunction and neuroprogression. 2. Review research on the relationship between several lifestyle-based factors and depression, and examine their effects on these depressogenic pathways. More specifically, the influence of diet, exercise, sleep, vitamin D, omega 3 essential fatty acid deficiency, stress and trauma, obesity and smoking were appraised along with their potential to prevent and treat major depression. The influence of psychological and pharmaceutical interventions on these dysregulated biological pathways was also reviewed. 3. Examine the antidepressant effects of curcumin. In animal-based models, curcumin has demonstrated antidepressant effects, although clinical studies are lacking. The efficacy of curcumin in an 8-week, randomised, double-blind, placebo-controlled study was examined in people with a major depressive disorder. Curcumin at a dose of 500 mg, twice daily, was compared with a placebo. The Inventory of Depressive Symptomatology-Self Report (IDS-SR30) and Spielberger State-Trait Anxiety Inventory were used to assess symptomatic change. Curcumin and placebo were equally effective in lowering depressive and anxiety symptomatology from baseline to week, but from weeks 4 to 8 curcumin supplementation was associated with superior antidepressant efficacy. 4. Review the potential role of peripheral biomarkers in major depression and examine biomarker changes following curcumin supplementation. Measurement of peripheral biomarkers has the potential to enhance diagnosis, evaluate treatment progress and facilitate treatment matching. In a randomised, double-blind, placebo controlled study, the influence of curcumin on several urinary, plasma and salivary peripheral biomarkers was examined. The efficacy of biomarkers to predict treatment efficacy from curcumin administration was also examined. Urinary leukotriene B4, thromboxane B2 and substance P were associated with changes following curcumin treatment, while higher baseline concentrations of plasma endothelin-1 and leptin were associated with greater treatment efficacy. Limitations associated with the clinical studies are reviewed and recommendations for future research are provided

A randomized, double-blind, placebo-controlled, crossover study examining the hormonal and vitality effects of ashwagandha (Withania somnifera) in aging, overweight males

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

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

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

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