Sex-Divergent Effects of Magnesium L-Threonate Supplementation on Sleep Quality, Cognitive Performance, and Neuromuscular Function in Healthy Adults

Sex-Divergent Effects of Magnesium L-Threonate Supplementation on Sleep Quality, Cognitive Performance Under Mental Fatigue, and Neuromuscular Function in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

This study examined the effects of six weeks of magnesium L-threonate (MgT) supplementation on sleep quality, cognitive performance under experimentally induced mental fatigue, neuromuscular function, and psychophysiological outcomes in healthy adults. Biological sex and weight status were examined as pre-specified moderating variables.

Study Overview

• Status: Completed
• Conditions: Healthy Adults; Cognitive Performance; Sleep Quality; Neuromuscular Function
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Magnesium L-threonate

Detailed Description

This study was a randomized, double-blind, placebo-controlled, parallel-group trial examining the effects of six weeks of magnesium L-threonate (MgT) supplementation on cognitive performance, mental fatigue, neuromuscular function, sleep quality, and psychophysiological outcomes in healthy adults. Biological sex and weight status were examined as pre-specified moderating variables given evidence for sex-specific differences in magnesium homeostasis and the elevated prevalence of magnesium inadequacy in individuals with overweight or obesity.

Participants:

Healthy male and female adults aged 18-45 years were recruited from a local university and surrounding community. Eighty-one participants were enrolled and randomized; the final analytic sample comprised 54 participants (MgT: n = 28; PLA: n = 26) following exclusions for non-adherence, technical data malfunction, and multivariate outlier removal. The sample was 59% female with a mean age of 23 ± 6 years and mean BMI of 26.7 ± 6.3 kg/m².

Intervention:

Participants assigned to the intervention group consumed 2 g·day-¹ of magnesium L-threonate (Magtein®; AIDP Inc., City of Industry, CA, USA) divided into two daily doses (morning and evening) for six weeks. Participants assigned to the placebo group consumed visually identical capsules containing rice powder (2 g·day-¹) on the same dosing schedule. Supplement compliance was assessed via capsule count at study conclusion; participants demonstrating less than 85% adherence were excluded from the final analytic sample.

Testing Procedures:

Participants completed identical testing sessions at baseline (Week 0) and following six weeks of supplementation (Week 6). All sessions were conducted at the same time of day for each participant to minimize circadian variability. Prior to each session, participants were instructed to abstain from caffeine for at least 12 hours, alcohol for 24 hours, and strenuous exercise for 24 hours.

Testing was conducted in a standardized order as follows:

Psychophysiological Questionnaires: Participants completed the Pittsburgh Sleep Quality Index (PSQI; 0-21 scale), Perceived Stress Scale (PSS), State-Trait Anxiety Inventory (STAI; state and trait subscales), and Visual Analog Scale for Fatigue (VAS-F; 0-100 mm) prior to any physical or cognitive testing.

Neuromuscular Assessment - Pre-fatigue: Countermovement jump (CMJ) performance was assessed using dual force plates (VALD ForceDecks, VALD Performance, Brisbane, Australia). Variables of interest included jump height (cm), peak landing force (N), reactive strength index (m·s-¹), and concentric impulse (N·s).

Cognitive Battery - Pre-fatigue: Cognitive performance was assessed using a computerized battery administered via the SOMA platform (SOMA Technologies, Lucerne, Switzerland). The battery included four tasks: the Psychomotor Fatigue Test (PFTT), Incongruent Flanker Task, Incongruent Stroop Task, and Task-Switching Test. Primary cognitive outcomes included reaction time (RT; ms), processing speed (1000/RT; s-¹), coefficient of variation (%), and rate correct score (correct responses·s-¹) derived from each task.

Mental Fatigue Induction: Mental fatigue was induced via a standardized 20-minute time-load dual-back (TLDB) task. The VAS-F was administered immediately before and after the TLDB task to quantify changes in perceived fatigue. The NASA Task Load Index (NASA-TLX) was completed immediately following the TLDB task to assess subjective cognitive workload across six subscales: mental demand, physical demand, temporal demand, performance, effort, and frustration.

Cognitive Battery - Post-fatigue: The full cognitive battery was repeated immediately following the TLDB protocol to assess performance under conditions of experimentally induced cognitive fatigue.

Neuromuscular Assessment - Post-fatigue: CMJ testing was repeated following the post-fatigue cognitive battery to assess the effect of cognitive load on subsequent neuromuscular output.

Statistical Analysis All analyses were performed in R with statistical significance set at α = 0.05. Primary outcomes were analyzed across three structurally distinct approaches: (1) absolute outcomes and within-bout change scores (pre- to post-mental fatigue) at W0 and W6 were analyzed using linear mixed models with fixed effects of condition, time, the condition-by-time interaction, and a random intercept for participant; (2) six-week change scores (W6 - W0) were analyzed using ANOVA with fixed effects of condition, sex, weight status, and the corresponding two- and three-way interactions; and (3) the change in the within-bout mental fatigue response across the six-week period was analyzed using analogous ANOVA to isolate whether MgT altered the magnitude of the acute mental fatigue response over time. Significant interaction effects were further assessed using post hoc comparisons with Bonferroni-Holm adjustment. Unadjusted simple effects tests were conducted when omnibus interactions were significant but adjusted post hoc comparisons were not, and are reported as exploratory. All primary models were re-estimated following removal of values exceeding ±3 SD to evaluate robustness of findings.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami Shores, Florida, United States, 33161
      • Barry University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male or female adults aged 18-45 years
• Free from diagnosed neurological, cardiovascular, metabolic, or psychiatric conditions
• Not currently taking medications or supplements known to influence cognitive or neuromuscular function
• Willing to maintain habitual diet, physical activity, and sleep routines throughout the study period

Exclusion Criteria:

• Pregnant or breastfeeding
• Diagnosed sleep disorder
• Initiated any new supplement or medication regimen within the past three months
• Failed to meet ≥85% supplementation adherence threshold during the study (post-enrollment exclusion)
• Technical data malfunction resulting in unrecoverable testing data (post-enrollment exclusion)
• Identified as a multivariate outlier (values exceeding ±3 SD from the group mean on primary outcomes; post-enrollment exclusion)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magnesium L-Threonate (MgT); Participants consumed 2 g·day-¹ of magnesium L-threonate (Magtein®; AIDP Inc., City of Industry, CA, USA) once daily for six weeks.	Dietary supplement: Magnesium L-threonate; Magnesium L-threonate; Other Names: Magtein®
Placebo Comparator: Placebo; Participants consumed visually identical capsules containing rice powder (1.4 g·day-¹) once daily for six weeks. Capsules were matched to the intervention in appearance and dosing schedule.	Dietary supplement: Placebo; Rice powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pittsburgh Sleep Quality Index (PSQI)	Subjective sleep quality assessed using the Pittsburgh Sleep Quality Index (PSQI; scored 0-21). Higher scores indicate poorer sleep quality. A score ≥5 indicates poor sleep quality.	Baseline (Week 0) and post-intervention (Week 6)
Flanker Task Reaction Time	Reaction time (ms) on the Incongruent Flanker Task assessed via computerized cognitive battery (SOMA platform). Lower values indicate faster processing.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after a 20-minute mental fatigue induction protocol at each visit
Countermovement Jump Height	Jump height (cm) assessed via dual force plates (VALD ForceDecks). Higher values indicate greater neuromuscular performance.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after a 20-minute mental fatigue induction protocol at each visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flanker Task Processing Speed	Processing speed (1000/RT; s-¹) on the Incongruent Flanker Task. Higher values indicate faster processing.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Flanker Task Rate Correct Score	Rate correct score (correct responses·s-¹) on the Incongruent Flanker Task. Higher values indicate better integrated speed-accuracy performance.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Flanker Task Coefficient of Variation	Intraindividual response variability (%) on the Incongruent Flanker Task. Lower values indicate more consistent performance.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Stroop Task Reaction Time	Reaction time (ms) on the Incongruent Stroop Task assessed via computerized cognitive battery. Lower values indicate faster processing.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Stroop Task Processing Speed	Processing speed (1000/RT; s-¹) on the Incongruent Stroop Task. Higher values indicate faster processing.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Stroop Task Rate Correct Score	Rate correct score (correct responses·s-¹) on the Incongruent Stroop Task. Higher values indicate better integrated speed-accuracy performance.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Psychomotor Fatigue Test Reaction Time	Reaction time (ms) on the Psychomotor Fatigue Test (PFTT). Lower values indicate faster psychomotor processing.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Psychomotor Fatigue Test Processing Speed	Processing speed (1000/RT; s-¹) on the PFTT. Higher values indicate faster psychomotor processing.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Psychomotor Fatigue Test Rate Correct Score	Rate correct score (correct responses·s-¹) on the PFTT. Higher values indicate better integrated speed-accuracy performance.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Task-Switching Test Reaction Time	Reaction time (ms) on the Task-Switching Test (TSWT). Lower values indicate faster cognitive flexibility.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Task-Switching Test Processing Speed	Processing speed (1000/RT; s-¹) on the TSWT. Higher values indicate faster cognitive flexibility.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Task-Switching Test Rate Correct Score	Rate correct score (correct responses·s-¹) on the TSWT. Higher values indicate better integrated speed-accuracy performance.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Time-Load Dual-Back Rate Correct Score	Rate correct score (correct responses·s-¹) on the 20-minute time-load dual-back (TLDB) mental fatigue induction task.	Baseline (Week 0) and post-intervention (Week 6)
Countermovement Jump Peak Landing Force	Peak landing force (N) assessed via dual force plates (VALD ForceDecks).	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Countermovement Jump Reactive Strength Index	Reactive strength index (m·s-¹) assessed via dual force plates (VALD ForceDecks). Higher values indicate greater neuromuscular efficiency.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Countermovement Jump Concentric Impulse	Concentric impulse (N·s) assessed via dual force plates (VALD ForceDecks). Higher values indicate greater force application during the propulsive phase.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction
Pittsburgh Sleep Quality Index - Global Score Change	Six-week change in PSQI global score stratified by sex and weight status.	Change from baseline (Week 0) to post-intervention (Week 6)
Perceived Stress Scale (PSS)	Perceived psychological stress assessed using the 10-item Perceived Stress Scale (scored 0-40). Higher scores indicate greater perceived stress.	Baseline (Week 0) and post-intervention (Week 6)
State-Trait Anxiety Inventory - State Subscale (STAI-S)	State anxiety assessed using the STAI state subscale (scored 20-80). Higher scores indicate greater anxiety.	Baseline (Week 0) and post-intervention (Week 6)
State-Trait Anxiety Inventory - Trait Subscale (STAI-T)	Trait anxiety assessed using the STAI trait subscale (scored 20-80). Higher scores indicate greater dispositional anxiety.	Baseline (Week 0) and post-intervention (Week 6)
Visual Analog Scale for Fatigue (VAS-F)	Subjective fatigue assessed using a 100 mm visual analog scale. Higher scores indicate greater perceived fatigue.	Baseline (Week 0) and post-intervention (Week 6), assessed before and after mental fatigue induction at each visit
NASA Task Load Index (NASA-TLX)	Multidimensional subjective workload assessed across six subscales: mental demand, physical demand, temporal demand, performance, effort, and frustration (each scored 0-20; total scored 0-120). Higher scores indicate greater perceived workload.	Baseline (Week 0) and post-intervention (Week 6), assessed immediately following mental fatigue induction

Collaborators and Investigators

• Sponsor: Barry University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Actual): March 19, 2026
• Study Completion (Actual): March 19, 2026

Study Registration Dates

• First Submitted: July 11, 2026
• First Submitted That Met QC Criteria: July 11, 2026
• First Posted (Actual): July 15, 2026

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 11, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: sex differences; cognitive performance; sleep quality; mental fatigue; neuromuscular function; countermovement jump; magnesium L-threonate; ergogenic supplementation
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Fatigue; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Sleep Initiation and Maintenance Disorders; Mental Fatigue; threonic acid
• Other Study ID Numbers: 2368924-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data may be made available upon reasonable request to the corresponding author, pending review of the proposed use and confirmation that appropriate data sharing agreements are in place.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No