Adrian Lopresti

Ashwagandha supplementation has been associated with reduced self-reported stress and anxiety, although most trials have used doses of 250-600 mg daily for 6-8 weeks. This study examined the effects of a low-dose ashwagandha extract (Ashwa.30™) on perceived stress, mood, fatigue, and stress reactivity in stressed adults.
In this 28-day, randomised, double-blind, placebo-controlled trial, 60 adults aged 18-65 years with self-reported stress were randomly allocated to receive ashwagandha 30 mg/day or placebo. Outcomes included the Depression, Anxiety, and Stress Scale, daily mood ratings, and the Chalder Fatigue Scale. The Socially Evaluated Cold-Pressor Test (SECPT) was conducted on Days 7 and 28, with subjective stress and fatigue, cardiovascular and electrodermal measures, skin temperature, and salivary cortisol and chromogranin A assessed.
Compared to the placebo, ashwagandha intake was associated with greater reductions in self-reported stress in the full analysis set (primary analysis; p = 0.046). The per protocol set analysis was directionally consistent but not statistically significant. Mean daily stress ratings were also lower in the ashwagandha group (p = 0.043). During the Day 28 SECPT, the ashwagandha group reported lower stress ratings (p = 0.044), and salivary cortisol concentrations remained relatively stable in the ashwagandha group but increased in the placebo group, suggesting attenuation of cortisol reactivity (p = 0.047). However, no statistically significant between-group differences were detected for other secondary and physiological outcomes.
An ashwagandha extract (Ashwa.30™) administered at 30 mg daily was associated with reduced self-reported stress in the Full Analysis Set and attenuation of SECPT-related salivary cortisol reactivity. These preliminary findings support further investigation in larger, adequately powered trials.
Australian and New Zealand Clinical Trials Registry: (ACTRN12625000129482) https://www.anzctr.org.au/ACTRN12625000129482p.aspx .

Magnesium supplementation is commonly used to support sleep, but evidence remains mixed. This review evaluated randomized controlled trials of oral magnesium administered as a stand-alone intervention for sleep-related outcomes in adults. PubMed/MEDLINE, Scopus, Cochrane CENTRAL, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform were searched from inception to 1 June 2026. Eligible studies were randomized controlled trials evaluating magnesium as the only active intervention, or including a magnesium-only arm, and reporting at least one sleep-related outcome in adults. Trials involving nocturnal leg cramps, restless legs syndrome, or periodic limb movements were synthesized separately. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach, and findings were synthesized narratively because of study heterogeneity. Twelve randomized controlled trials were included in the main synthesis on sleep, insomnia, or poor sleep, and three additional trials involving movement- or cramp-related sleep disturbance were analyzed separately. One separately analyzed restless legs syndrome trial enrolled participants aged 15-50 years because adult-only data were unavailable. Populations, magnesium formulations, elemental doses, treatment durations, outcome roles, and measures varied substantially. Findings were inconsistent across subjective outcomes, EEG, research-grade actigraphy, consumer wearable-derived estimates, and physiological markers. Certainty of evidence was low to very low. Current evidence does not support oral magnesium as a routine treatment for insomnia. It may provide modest benefits for selected subjective outcomes in some adults, but the findings are inconsistent, and the certainty of the evidence is low or very low. Further well-designed, adequately powered trials are required before routine recommendations can be made.

Studies in adults have demonstrated that lutein and zeaxanthin (LZ) supplementation may improve eye and cognitive function, although limited studies have been conducted in teenagers. In this two-arm, 6-month, parallel-group, randomized, double-blind, placebo-controlled trial, supplementation with a placebo (sunflower oil) or lutein (10 mg) and zeaxanthin (2 mg) was examined for its effects on macular pigment optical density (MPOD), cognitive function, and sleep in teenagers aged 13 to 18 years with high screen use and consuming a diet low in fruits and vegetables. Eighty-two teenagers were assigned to receive LZ or a placebo daily. Outcome measures included changes in MPOD (primary outcome), cognitive performance (Test of Memory and Learning Version 2, National Institute of Health Cognition Toolbox, and 3D Aim Trainer), and self-report measures of attention and sleep. It was hypothesized that LZ supplementation would be associated with increases in MPOD and improvements in cognitive function. Compared to the placebo, LZ were associated with greater improvements in MPOD in the left (P = .010) and right eyes (P = .004), tests of attention (P = .026) and processing speed (P = .034), but not in the test of visual reasoning (P = .728), nonverbal memory (P = .999), or a first-person shooter game (P = .873). Moreover, there were no between-group differences in changes in self-report measures of attention and sleep. LZ supplementation was well-tolerated with no significant adverse reactions reported. This is the first published study to demonstrate that supplementation with LZ in teenagers for 6 months can increase MPOD and some aspects of cognitive performance. Further research on teenagers with impairments in cognitive performance and sleep quality will be important to extend the results of this study.

Trial registration: This trial was registered prospectively on January 20, 2025 with the Australian and New Zealand Trials Registry (ANZCTR) (ACTRN12625000047493).
Eighty-two adolescents aged 13 to 18 years were randomized to receive lutein and zeaxanthin (10 mg/2 mg daily) or placebo for 6 months. Supplementation increased macular pigment optical density and improved attention and processing speed compared with placebo. No significant effects were observed for visual reasoning, nonverbal memory, sleep, or gaming performance. Lutein and zeaxanthin may support visual and cognitive function during adolescence. [Display omitted]

Background: Depression is commonly accompanied by sleep disturbances and low self-esteem. Saffron (Crocus sativus L.) has demonstrated antidepressant and sleep-enhancing effects in previous clinical trials; however, its efficacy in women experiencing both low mood and poor sleep has not been specifically examined. Furthermore, the effects of saffron on self-esteem and skin health remain largely unexplored.Objective: To examine the effects of supplementation with a saffron extract (Affron®) on mood, sleep, self-esteem, and skin health in women aged 50–70 years experiencing low mood and self-reported poor sleep.Methods: In this randomised, double-blind, placebo-controlled trial, 86 women were allocated in a 1:1 ratio to receive either 28 mg/day of a saffron extract or placebo for 12 weeks. The primary outcome was the Depression, Anxiety and Stress Scale–21 (DASS-21) depression subscale. Secondary outcomes included the PROMIS Sleep Disturbance and Sleep-Related Impairment scales, the Rosenberg Self-Esteem Scale, a self-report measure of physical appearance, and facial skin age estimated using an artificial intelligence–based application.Results: Compared with placebo, saffron resulted in greater reductions in DASS-21 depression scores (adjusted mean difference: 2.37; 95% CI: 0.23, 4.51; d = 0.48, p = 0.030). A clinically meaningful improvement in depressive symptoms (≥7-point reduction) was achieved by 48.8% of participants receiving saffron compared with 25.6% receiving placebo (p = 0.026). Saffron was also associated with greater improvements in self-esteem (adjusted mean difference: 1.43; 95% CI: 0.22, 2.64; d = 0.51; p = 0.022) and sleep-related impairment (adjusted mean difference: 2.99; 95% CI: 0.12, 5.86; d = 0.45; p = 0.041). No significant between-group differences were observed for sleep disturbance (p = 0.786), self-rated physical appearance (p = 0.964), or estimated facial skin age (p = 0.473). Saffron was well tolerated, with no serious adverse events reported.Conclusion: Supplementation with a saffron extract (Affron®) for 12 weeks was associated with improvements in depressive symptoms. Improvements were also observed in self-esteem and sleep-related impairment; however, these secondary findings should be considered exploratory and require confirmation in adequately powered studies. No significant group differences were observed for sleep disturbance, perceived physical appearance, or estimated facial skin age.

Background Khaya senegalensis is a tree species that has traditional use for the alleviation of menstrual and hormonal symptoms in women. Moreover, supplementation with a Khaya senegalensis preparation (Khapregesic (R)) was associated with significant and rapid improvements in menstrual pain, mood, sleep, and fatigue in women with menstrual distress over 28 days. The present study aimed to assess the safety and efficacy of Khapregesic (R) over the same intervention period in women reporting menopausal symptoms across the transition from perimenopause to post-menopause.Methods In this 28-day, randomised, double-blind, placebo-controlled study, 140 peri- and postmenopausal women aged 42-62 years experiencing menopausal-related symptoms were supplemented with 2 grams daily of Khapregesic (R) or a matching placebo. Outcomes were assessed using validated self-report measures of menopausal symptoms (primary outcome: Greene Climacteric Scale), sleep disturbance/sleep-related impairment (PROMIS-Sleep Scale), fatigue (FACIT-Fatigue), vasomotor symptoms (hot flush rating scale), and digestive symptoms, alongside tolerability and safety monitoring.Results There were no statistically significant group differences in change scores across the primary and secondary outcomes. However, stratified analyses by menopausal stage indicated in postmenopausal women (n = 69), Khapregesic (R) was associated with significantly greater improvements versus placebo in psychological symptoms (p = 0.014), fatigue (p = 0.045), and sleep disturbances (p = 0.024). In contrast, no group differences were detected in perimenopausal women (n = 71). Khapregesic (R) for 28 days was generally well tolerated, with a tendency towards transient, mild gastrointestinal symptoms.Conclusions Based on data from the full cohort, no statistically significant group effects were observed in this study. Subgroup analyses revealed positive improvements in post-menopausal but not perimenopausal women in mood/psychological symptoms, sleep disturbance, and fatigue. However, these secondary analyses should be considered tentative and require confirmation in future trials. Clinical Trial Registration: https://anzctr.org.au/ACTRN12625000247471p.aspx, identifier ACTRN12625000247471p.Conclusions Based on data from the full cohort, no statistically significant group effects were observed in this study. Subgroup analyses revealed positive improvements in post-menopausal but not perimenopausal women in mood/psychological symptoms, sleep disturbance, and fatigue. However, these secondary analyses should be considered tentative and require confirmation in future trials. Clinical Trial Registration: https://anzctr.org.au/ACTRN12625000247471p.aspx, identifier ACTRN12625000247471p.

The oral delivery of curcumin has been shown in several studies to have beneficial pain-relieving effects for the treatment of knee osteoarthritis. However, there has been limited investigation into its efficacy and tolerability when delivered topically. The purpose of this two-arm, 28-day, parallel-group, randomised, double-blind, placebo-controlled trial was to determine the effects of a topical curcumin gel (VAS-101) on knee pain and symptoms in adults with knee osteoarthritis.
Sixty adults aged 45-75 with knee osteoarthritis applied a curcumin or placebo gel to their knee, every second day for 28 days. Outcome measures comprised the Knee Injury and Osteoarthritis Outcome Score (KOOS), daily pain ratings, and several performance-based tests. Rescue oral medication intake was also monitored over time.
Compared to the placebo, VAS-101 was associated with greater improvements in the KOOS pain score (primary outcome measure) (β: 5.12; 95% CI: 0.47, 9.77; d = 0.62,
 = 0.041), and mean daily pain ratings (F
 = 4.42; d = 0.55,
 = 0.005). In the VAS-101 group, 39.3% of participants reported feeling either much or very much improved, compared with 13.3% in the placebo group (
 = 0.019). Moreover, 32.1% of participants in the VAS-101 group achieved a Minimal Clinically Important Difference, compared to 13.3% in the placebo group, although this group difference was not statistically significant (
 = 0.086). There were no group differences in changes in other KOOS subscale scores or the performance-based tests. VAS-101 was well-tolerated, with no significant adverse reactions reported. However, skin staining was observed as expected with topical curcumin, which resolved 2-3 days after application ceased.
Conservative dosing of a topically applied curcumin-containing gel (VAS-101), administered every two days for 28 days, is associated with moderate reductions in knee pain in adults with knee osteoarthritis. Further investigations utilising larger sample sizes, longer treatment durations, and alternative treatment regimens will be important to identify how these factors affect treatment adherence, tolerance, and efficacy.

Background/objectives: Magnesium may help support cognition and sleep. The purpose of this two-arm, 6-week, parallel-group, randomised, double-blind, placebo-controlled trial was to examine the effects of magnesium L-threonate (Magtein®) supplementation on cognitive performance, cognitive age, sleep quality, and selected physiological indicators in adults.

Methods: One hundred adults aged 18 to 45 with self-reported dissatisfied sleep were supplemented with 2 g daily of Magtein® or a placebo. Outcome measures comprised the computer-based National Institute for Health (NIH) Cognitive Toolbox and Raven’s Progressive Matrices Version 2 for the assessment of cognitive function, self-report evaluations of sleep quality and emotional wellbeing, a reaction time test, and physiological data obtained from a sleep-tracking wearable device (Oura Ring), including resting heart rate (HR) and heart rate variability (HRV) during sleep.

Results: Compared to the placebo, Magtein® was associated with greater improvements in overall cognitive performance as measured by the NIH Total Cognition Composite (p = 0.043), with larger treatment effects on working and episodic memory. There was also a 7.5-year reduction in estimated brain cognitive age and a greater improvement in reaction time (p = 0.031). However, there were no group differences in changes in the Raven’s test (p = 0.953). Based on self-report measures, there was a greater improvement in sleep-related impairment (p = 0.043), but no group differences in changes in sleep disturbances (p = 0.316), restorative sleep (p = 0.439), or general wellbeing (p = 0.436); although in a subset of participants with more severe sleep-related problems, group differences in sleep-disturbances were identified (p = 0.031). Based on data from the sleep tracking ring, there were no group differences in sleep outcomes, although there was a greater reduction in HR (p = 0.030) and an increase in HRV (p = 0.036), a physiological marker of stress reduction and improved autonomic balance. Magtein® was well-tolerated, and there were no reports of significant adverse reactions.

Conclusion: The results from this study suggest Magtein® supplementation for 6 weeks improves overall cognition, cognitive age, working memory, reaction time, HR, HRV, and some subjective, but not objective measures of sleep in healthy adults with self-reported dissatisfied sleep.

Background and Objectives
Bacopa monnieri is a plant used in Ayurvedic medicine with traditional uses for memory and cognitive function. The objective of this study was to examine the effects of supplementation with a Bacopa monnieri extract (Bacumen®) on cognitive function, stress, and fatigue in adults with self-reported memory and attention problems.

Study Design
Two-arm, 12-week, parallel-group, randomized, double-blind, placebo-controlled trial.

Methods
Overall, 101 volunteers aged 40–70 years with self-reported memory and attention problems were supplemented with 300 mg daily of a Bacopa monnieri extract (Bacumen®) (n = 50) or a placebo (n = 51). Outcome measures included several computer and researcher-administered cognitive tasks assessing verbal learning, attention and working memory (primary outcome measures) and self-report measures assessing memory, mood, and fatigue (secondary outcome measures). Changes in blood concentrations of brain-derived neurotrophic factor, malondialdehyde, and acetylcholine esterase activity were also examined. Cognitive assessments, blood collections and self-reported questionnaires were completed in person on day 0 and week 12. Moreover, self-report questionnaires were completed online at weeks 4 and 8. Participants, researchers and the statistician were blinded until all data was collected and a blind review was completed.

Results
Of the 101 participants randomized, 87 participants completed the study, 47 in the placebo group and 40 in the Bacopa monnieri group. On the basis of complete data collected from 87 participants, there were no between-group differences in changes in the primary outcome measures comprising verbal learning (p = 0.391), attention (p = 0.713), and working memory (p = 0.610). However, in the Bacopa-supplemented participants, there were greater reductions in overall self-reported stress reactivity (p = 0.03); and fatigue and stress levels after exposure to a cognitive-demanding computer task (secondary outcome measures). There were no group differences in changes in blood concentrations of measured markers. Bacopa monnieri supplementation was generally well-tolerated, with no serious adverse reactions, although there was a greater frequency of self-reported adverse reactions in the Bacopa monnieri group (p = 0.024), primarily comprising digestive complaints and headaches.

Conclusions
The results from this study indicate that compared with the placebo, Bacopa monnieri supplementation for 12 weeks did not result in greater improvements in cognitive performance. However, stress reduction and anti-fatigue effects were identified, which requires investigation in future trials.

Clinical Trials Registration Number
Australian New Zealand Clinical Trials Registry (ANZCTR)—ACTRN12623000475640.

Background/objectives: Tocotrienols are a form of vitamin E that may have neuroprotective effects. However, there have been no studies examining its effects on cognitive function when delivered as a stand-alone intervention. The purpose of this two-arm, 12-week, randomised, double-blind, placebo-controlled trial was to examine the effects of supplementation with tocotrienols derived from rice bran (TheraPrimE® rice) on memory and sleep in adults with subjective memory complaints.

Methods: Ninety-one adults aged 40–80 were supplemented with a placebo or 100 mg of tocotrienols daily. Outcome measures included the Test of Memory and Learning (version 2), and self-report questionnaires assessing executive function and sleep quality. Moreover, changes in blood markers associated with inflammation, oxidative stress, and neurotropic activity were examined.

Results: Compared to the placebo, tocotrienol supplementation was associated with greater improvements in general memory (p = 0.045, 95% CI: 0.34, 32.21). Memory changes were primarily due to improvements in non-verbal memory (p = 0.039, 95% CI: 0.68, 26.63). However, there were no group differences in changes in verbal memory. Moreover, there were no group differences in changes in self-reported executive function, although there were greater improvements in sleep disturbance in the tocotrienols group (p = 0.015, 95% CI: −4.80, −0.55). An examination of blood markers revealed a statistically significant larger increase in Tumour Necrosis Factor-α in the placebo group (p = 0.043) and a larger increase in C-reactive protein (p = 0.039) in the tocotrienols group. Tocotrienols were not associated with any serious adverse reactions.

Conclusion: This is the first controlled study demonstrating the cognitive-enhancing and sleep-promoting effects of stand-alone supplementation with tocotrienols. However, future research is required to substantiate this study’s results and examine the potential mechanisms of action.

Purpose: To assess the effects of magnesium bisglycinate supplementation on insomnia symptoms in healthy adults reporting poor sleep quality.
Patients and Methods: This randomized, double-blind, placebo-controlled trial enrolled 155 adults aged 18– 65 years with self-reported poor sleep quality. Participants were randomly assigned to either magnesium bisglycinate supplementation (250 mg elemental magnesium, daily) or placebo capsules. Sleep quality was assessed using the Insomnia Severity Index (ISI) and additional psychological questionnaires at baseline and multiple time points throughout the study. Generalized linear mixed models (GLMM) adjusted for baseline ISI scores, age, sex, body mass index, and occupation were applied.

Results: The magnesium bisglycinate group showed a significantly greater reduction in ISI scores compared to the placebo group from baseline to Week 4 (− 3.9 [95% CI: − 5.8 to − 2.0] vs − 2.3 [95% CI: − 4.1 to − 0.4], respectively; p = 0.049). The effect size was small (Cohen’s d = 0.2), indicating a modest benefit. Exploratory analyses suggested notably greater improvements among participants reporting lower baseline dietary magnesium intake, potentially indicating a subgroup of high responders. No significant differences were observed in other psychological outcomes.

Conclusion: Magnesium bisglycinate supplementation modestly improved insomnia severity in adults reporting poor sleep quality. Future research should include objective sleep assessments, longer intervention periods, and better characterization of potential high responders by systematically assessing baseline dietary magnesium intake and status.
Clinical Trial Registration Name: Effect of magnesium bisglycinate supplementation on sleep and fatigue parameters in healthy adults reporting poor sleep quality; https://drks.de/search/en/trial/DRKS00031494 DRKS-ID: DRKS00031494.