Participants
Participants were 31 nonobese adults (M age = 46.01, SD = 8.47; range = 27 to 55 years; M BMI = 25.23 6.66) who reported nonclinical insomnia symptoms based on the Insomnia Severity Index (M = 13.10, SD = 4.10) [7].
Exclusion Criteria
Participants were excluded if they had severe insomnia (based on the Insomnia Severity Index ≥ 22) or absence of insomnia ( < 8); (2) history of a disorder affecting sleep quality; (3) events that could cause severe stress within 2 weeks of baseline; (4) use of medication that could influence sleep patterns, within 1 month of baseline; (5) current use of hormone therapy; (6) binge drinking; (7) smoking; (8) high caffeine intake; (9) work schedule that causes irregular sleep patterns; (10) history of travel to a different time zone within 1 month of study; (11) low or high body mass index (BMI ≤ 18 kg/m2 or ≥30 kg/m2); (12) pregnant, trying to conceive, or breastfeeding; (13) taking sleep supplements or medication, (14) unwilling to abstain from other magnesium product use for two weeks leading up to trial initiation and during the trial, and (14) individuals deemed incompatible with the study protocol.
Procedures
Based on the prescreen questionnaire, eligible participants signed an Institutional Review Board approved informed consent prior to enrolling in the study. Participants completed psychometrically validated self-report questionnaires at Day 0 (Pre) and post each condition. Participants also completed a Daily Diary to assess subjective sleep quality/quantity, adherence, and adverse events, and wore an Oura Ring to objectively determine sleep and daytime activity. Participants maintained their current lifestyle behaviors and did not engage in any new forms of structured exercise or begin a new diet or health intervention during the trial. The adherence rate was 100%.
Study design: This study was approval by Sterling Institutional Review Board (10721-HAHausenblas) in compliance with the Declaration of Helsinki standards for ethical principles regarding human participant research and registered with ISRCTN registry is ISRCTN70584524. The Consolidated Standards of Reporting Trials (CONSORT) was used to report this trial.
This study was conducted in a double-blind, parallel treatment, stratified random, placebo-controlled manner. The independent variable was the UF Magnesium nutritional supplementation. The dependent variables were sleep quality and quantity. Sample size power calculation indicated that 30 participants were needed in each group to achieve a power of 80% and alpha < .05 (https://clincalc.com/stats/samplesize.aspx).
Intervention: Using a randomized double-blind placebo-controlled crossover pilot trial, the participants were randomized to either the Magnesium or Placebo Control condition for 2 weeks. Following a one-week washout period, the participants engaged in the alternate condition. The magnesium (i.e., Upgraded Formulas) was a nano magnesium chloride that is 100% natural, keto, organic, and vegan. It is free from artificial flavors, fillers, colors, and stabilizers. Participants were instructed to take 4 capsules 120 minutes or less before bed with 12 oz of water. The Placebo was sucrose.
Blinding: To ensure that all subjects and researchers were unaware of the treatment assignments, the supplement/placebo bottles were labelled as either A or B by an independent party. The supplement/placebo pills were identical in color, odor, and size. The research team was blinded to the content of the bottles. At the conclusion of the study, immediately following the last assessment, the research team was unblinded. The participants were then unblinded and informed of their assigned condition.
Supplement Information and Adherence: Participants were instructed to take the capsules about 30 minutes prior to nighttime sleep. The participants provided the number of pills remaining in their bottles as an adherence measure as well as indicated their adherence. The participants also received a daily text reminder to take their supplement.
Measures
The following psychometrically validated self-report measures were completed at Baseline and Post Conditions:
Insomnia Severity Index: The Insomnia Severity Index is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia[7]. The dimensions evaluated are: severity of sleep onset, sleep maintenance, and early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by the sleep difficulties. A 5-point Likert scale is used to rate each item (e.g., 0 = no problem; 4 = very severe problem), yielding a total score ranging from 0 to 28. The total score is interpreted as follows: absence of insomnia (0–7); sub-threshold insomnia (8–14); moderate insomnia (15–21); and severe insomnia (22–28).
Pittsburgh Sleep Quality Index. The Pittsburgh Sleep Quality Index is a standardized, self-administered questionnaire that evaluates retrospective sleep quality and disturbances within the past month [8]. The translated PSQI consists of the same items as the original instrument; it comprises 19 items forming seven subscales: (1) sleep quality (1 item), (2) sleep latency (2 items), (3) sleep duration (1 item), (4) sleep efficiency (3 items), (5) sleep disturbance (9 items), (6) sleep medication (1 item), and (7) daily dysfunction (2 items). The PSQI-M was evaluated following the original scoring system. Each component has a score that ranges from 0 to 3. The scores of seven components will be summed to yield a PSQI global score ranging from 0 to 21. Respondents with a global score of greater than 5 are classified as ‘poor sleepers’, while those with a score of 5 or less are classified as ‘good sleepers’.
Restorative Sleep Questionnaire: The Restorative Sleep Questionnaire (RSQ) is a validated 11-item questionnaire that assesses restorative sleep by asking respondents to rate on a 5-point scale feelings of tiredness, mood, and energy [10]. The RSQ has good psychometric properties and is able to distinguish between healthy controls, patients with primary insomnia, and insomnia patients with isolated nonrestorative sleep complaints.
Profile of Mood States (POMS) Questionnaire: The POMS-40 was used to assess the mood states of tension, anger, vigor, fatigue, depression, and confusion [11]. A composite score was computed by summing each of the individual scores for tension, depression, anxiety, fatigue, and confusion, with vigor scores subtracted to indicate patients' total mood disturbance. Each item of the POMS items was scored on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely) with lower scores indicated an improved mood. This scale has good to excellent reliability and validity [11].
Flinders Fatigue Scale: The Finders Fatigue Scale is a 7-item scale that measures various characteristics of fatigue (e.g., frequency, severity) experienced over the past 2 weeks [12]. The items tap into commonly reported themes of how problematic fatigue is, the consequences of fatigue, frequency, severity, and insomnia patients' perception of fatigue's association with sleep. Six items are presented in Likert format, with responses ranging from 0 (not at all) to 4 (extremely). Item 5 measures the time of day when fatigue is experienced and uses a multiple-item checklist. Respondents can indicate more than one response for item 5, and it is scored as the sum of all times of the day indicated by the respondent. One item explicitly asks for respondents' impression of whether they attribute their fatigue to their sleep. Total fatigue is calculated as the sum of all individual items. Total fatigue scores range from 0 to 31, with higher scores indicating greater fatigue. A clear description of the term “fatigue” is provided in the initial instructions to the scale.
Perceived Stress Scale: The Perceived Stress Scale-4 measures the degree to which individuals appraise situations in their lives as stressful [13]. Specifically, the scale evaluates the degree to which individuals believe their life has been unpredictable, uncontrollable, and overloaded during the previous month. The items are general in nature rather than focusing on specific events or experiences. The scale consisted of four items, and each item was scored on a 5-point Likert scale ranging from 0 (“never”) to 4 (“very often”) with higher scores indicating more perceived stress. This scale has excellent psychometric properties (Du et al., 2023).
Pain and Sleep Questionnaire: The Pain and Sleep Questionnaire measures the impact of pain on sleep in chronic pain patients is the Pain and Sleep Questionnaire (PSQ) (14). The PSQ is an eight-item questionnaire developed to assess the impact of pain on quality of sleep. Six of the eight items are scored on a 100 mm VAS (ranging from 0 [‘never’] to 100 [‘always’]) and asks respondents to rate how often they have trouble falling asleep (PSQ1); how often they need pain medication to fall asleep (PSQ2); how often they need sleeping medication to fall asleep (PSQ3); how often they are awakened by pain during the night (PSQ4) and in the morning (PSQ5); and how often their partner is awakened (PSQ6). The seventh item is also scored using a VAS; however, it uses different anchor points (0 [‘very poor’], 100 [‘excellent’]) and asks individuals to rate the overall quality of their sleep. The final item asks individuals to indicate, using a number that can range from 1 to 24, the average number of hours of sleep they get each night. Typically, a single index is created from summing the scores on the first five items and using this composite score as an overall measure of the impact of pain on quality of sleep (referred to as the Pain and Sleep Index).
Trait Anxiety Inventory: The Trait Anxiety Inventory (20-items) was used to measure general feelings of anxiety including general states of calmness, confidence, and security [15]. Higher scores indicate more severe anxiety levels. Each item was assessed on a 4-point Likert-type scale (from 0 to 3 points).
Daily measures were:
Oura Ring. The Oura Ring is a novel, multisensory device that quantifies daily physical activity, night-time sleep duration, and estimates sleep stages, including REM (https://ouraring.com/). The ring also measures motion and body temperature. The Oura Ring uses physiological signals (a combination of motion, heart rate, heart rate variability, and pulse wave variability amplitude) in combination with sophisticated machine learning based methods to calculate deep, light and rapid-eye-movement (REM) sleep in addition to sleep/wake states. Rings are waterproof, made in ceramic, and come with a dedicated mobile App. They come in different sizes (US standard ring sizes 6–13) and weigh about 15 g with a battery life of about 3 days. The ring automatically connects via Bluetooth and transfers data to a mobile platform via the dedicated App. The Oura Ring has high validity in the assessment of nocturnal heart rate, heart rate variability, movement and sleep outcomes in healthy adults in natural environment [21]. Participants will keep the Oura Ring at the completion of the study.
Daily diary: The daily diary assessed adverse events and adherence.
Statistical Analysis: Data were analyzed for normality by examining skewness and kurtosis scores and using Shapiro-Wilk test and Q-Q plot. Outliers were characterized as data points that exceeded three interquartile ranges beyond 25th and 75th percentiles. However, no extreme outliers were observed. Descriptive statistics were expressed in Mean (SD). Paired sample t-tests (delta scores) were used to analyze time and condition differences for the self-report measures (p’s ≤ .05). For the Oura Ring data 2 (Condition: Magnesium x Placebo) x 3 (Time: Week 1, Week, 2,) repeated measures analysis of variance (ANOVA) were used to analyze the Oura Ring data. Multiple comparisons were corrected using Sidak Adjustment. Pos hoc tests were paired-sample t-tests where applicable. The data were analyzed using EXCEL and Statistical Product and Service Solutions (SPSS) version 28.