Submitted:
23 July 2024
Posted:
24 July 2024
You are already at the latest version
Abstract
Keywords:
1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Recruitment and Randomization
2.3. Participants
2.3.1. Inclusion Criteria
2.3.2. Exclusion Criteria
2.4. Interventions
2.5. Outcome Measures
2.5.1. Primary Outcome Measures
2.5.2. Secondary Outcome Measures
2.5.3. Exploratory Outcome Measures
2.5.4. Safety Outcome Measures
2.6. Sample Size Calculations
2.7. Statistical Analysis
3. Results
3.1. Study Population
3.2. Baseline Questionnaire and Demographic Information
3.3. Outcome Measures
3.3.1. Primary Outcome Measures
3.3.2. Secondary Outcome Measures
3.3.3. Exploratory Outcome Measures
3.4. Intake of Supplements
3.5. Efficacy of Participant Blinding
3.6. Adverse Reactions and Treatment Discontinuation
4. Discussion
4.2. Limitations and Directions for Future Research
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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| LZ (n=35) | Placebo (n=35) | p-value | ||
|---|---|---|---|---|
| Age | Mean | 48.26 | 46.07 | .449a |
| SE | 2.04 | 2.03 | ||
| Sex | Female (n) | 16 | 16 | 1.00b |
| Male (n) | 19 | 19 | ||
| Height (m) | Mean | 1.72 | 1.72 | .734a |
| SE | 0.01 | 0.02 | ||
| Weight (kg) | Mean | 77.29 | 76.50 | .799a |
| SE | 2.02 | 2.34 | ||
| BMI | Mean | 26.12 | 25.59 | .441a |
| SE | 0.45 | 0.51 | ||
| Systolic blood pressure (mmHg) | Mean | 123.77 | 123.03 | .833a |
| SE | 2.53 | 2.44 | ||
| Diastolic blood pressure (mmHg) | Mean | 77.69 | 79.11 | .571a |
| SE | 1.93 | 1.59 | ||
| Pulse (bpm) | Mean | 70.11 | 69.43 | .788a |
| SE | 1.69 | 1.89 | ||
| Marital status | Single | 15 | 14 | .808b |
| Married/ defacto | 20 | 21 | ||
| Educational level | Secondary | 20 | 14 | .348b |
| Tertiary | 8 | 12 | ||
| Post-graduate | 7 | 9 | ||
| International Physical Activity Questionnaires category | Low | 24 | 10 | .003b |
| Moderate | 10 | 21 | ||
| High | 1 | 4 | ||
| Occupation | Retired | 2 | 3 | .767b |
| Professional | 12 | 17 | ||
| Services and sales worker | 4 | 2 | ||
| Unemployed | 2 | 0 | ||
| Technicians and associated trades | 2 | 3 | ||
| Elementary occupation | 1 | 0 | ||
| Student | 2 | 3 | ||
| Clerical support worker | 3 | 2 | ||
| Craft and related trades worker | 1 | 1 | ||
| Manager | 6 | 4 | ||
| STT (mm) | Mean | 21.20 | 20.83 | .896b |
| SE | 2.06 | 1.95 | ||
| PSRT (sec) | Mean | 9.37 | 8.34 | .087a |
| SE | 2.49 | 1.61 | ||
| TBUT (sec) | Mean | 29.30 | 27.51 | .949a |
| SE | 3.77 | 3.43 | ||
| CS (decibel units) | Mean | 20.77 | 21.23 | .786a |
| SE | 0.34 | 0.26 | ||
| VA (metre) | Mean | 12.28 | 14.41 | .549a |
| SE | 2.21 | 2.76 | ||
| VFS total score | Mean | 11.77 | 10.40 | .552a |
| SE | 1.91 | 1.28 | ||
| CVS-Q total score | Mean | 8.40 | 6.06 | .145a |
| SE | 1.41 | 0.73 | ||
| PROMIS sleep disturbance (T-score) | Mean | 50.41 | 50.68 | .877a |
| SE | 1.36 | 1.09 | ||
| PROMIS sleep-related impairment (T-score) | Mean | 51.01 | 50.73 | .891a |
| SE | 1.64 | 1.28 | ||
| ELAS total score | Mean | 102.83 | 95.28 | .244a |
| SE | 4.95 | 4.11 | ||
| Day 0 | Day 90 | Day 180 | p-valuea | p-valueb | |||
|---|---|---|---|---|---|---|---|
| STT (mm) | Placebo (n = 31) | Mean | 21.19 | 20.94 | 19.38 | 0.136 | 0.024 |
| SE | 1.88 | 1.90 | 1.76 | ||||
| LZ (n = 29) | Mean | 20.66 | 19.70 | 22.74 | 0.123 | ||
| SE | 1.84 | 1.79 | 2.09 | ||||
| PSRT (sec) | Placebo (n = 31) | Mean | 9.10 | 11.49 | 11.36 | 0.116 | 0.063 |
| SE | 1.11 | 1.47 | 1.45 | ||||
| LZ (n = 29) | Mean | 9.72 | 8.62 | 7.91 | 0.143 | ||
| SE | 1.19 | 1.10 | 1.04 | ||||
| TBUT (sec) | Placebo (n = 31) | Mean | 28.21 | 30.57 | 27.30 | 0.694 | 0.031 |
| SE | 2.96 | 3.31 | 2.95 | ||||
| LZ (n = 29) | Mean | 25.51 | 28.53 | 33.00 | 0.005 | ||
| SE | 2.69 | 3.09 | 3.62 | ||||
| Contrast Sensitivity (db) | Placebo (n = 31) | Mean | 21.19 | 21.75 | 22.34 | 0.001 | 0.694 |
| SE | 0.24 | 0.27 | 0.27 | ||||
| LZ (n = 29) | Mean | 20.79 | 21.66 | 22.30 | < .001 | ||
| SE | 0.24 | 0.27 | 0.28 | ||||
| Visual acuity | Placebo (n = 31) | Mean | 0.664 | 0.646 | 0.627 | .148 | 0.258 |
| SE | 0.052 | 0.052 | 0.050 | ||||
| LZ (n = 29) | Mean | 0.768 | 0.740 | 0.782 | .646 | ||
| SE | 0.061 | 0.059 | 0.063 |
| Group | N | Mean change (day 0 to 180) | SE | 95% Confidence Interval | Cohen’s D Effect Size | P-value | ||
|---|---|---|---|---|---|---|---|---|
| Lower | Upper | |||||||
| STT (mm) | LZ | 29 | 2.09 | 1.18 | -0.27 | 4.45 | .66 | 0.015 |
| Placebo | 31 | -2.02 | 1.14 | -4.31 | 0.26 | |||
| PSRT (sec) | LZ | 29 | -1.45 | 1.23 | -3.92 | 1.01 | .62 | 0.023 |
| Placebo | 31 | 2.58 | 1.19 | 0.19 | 4.96 | |||
| TBUT (sec) | LZ | 29 | 8.50 | 2.81 | 2.86 | 14.13 | .63 | 0.020 |
| Placebo | 31 | -0.90 | 2.72 | -6.36 | 4.55 | |||
| Contrast Sensitivity (db) | LZ | 29 | 1.32 | 0.23 | 0.86 | 1.79 | .19 | 0.719 |
| Placebo | 31 | 1.44 | 0.22 | 0.99 | 1.89 | |||
| Visual acuity | LZ | 29 | 0.034 | 0.024 | -0.014 | 0.082 | .59 | 0.028 |
| Placebo | 31 | -0.041 | 0.023 | -0.088 | 0.005 | |||
| Day 0 | Day 30 | Day 60 | Day 90 | Day 120 | Day 150 | Day 180 | p-valuea | p-valueb | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| VFS | Placebo (n = 31) | Mean | 10.38 | 6.98 | 6.21 | 6.44 | 4.73 | 4.31 | 4.76 | < .001 | 0.312 |
| SE | 1.43 | 1.43 | 1.45 | 1.45 | 1.45 | 1.45 | 1.45 | ||||
| LZ (n = 29) | Mean | 11.54 | 11.17 | 8.38 | 9.25 | 8.04 | 7.76 | 7.43 | < .001 | ||
| SE | 1.43 | 1.44 | 1.44 | 1.46 | 1.47 | 1.47 | 1.47 | ||||
| CVS-Q | Placebo (n = 31) | Mean | 6.06 | 5.40 | 4.72 | 4.81 | 3.98 | 4.01 | 3.98 | 0.005 | 0.575 |
| SE | 1.02 | 1.02 | 1.04 | 1.04 | 1.04 | 1.04 | 1.04 | ||||
| LZ (n = 29) | Mean | 8.17 | 8.36 | 6.27 | 6.03 | 5.43 | 4.99 | 5.49 | < .001 | ||
| SE | 1.02 | 1.04 | 1.04 | 1.04 | 1.04 | 1.04 | 1.06 | ||||
| ELAS | Placebo (n = 31) | Mean | 95.15 | - | 96.23 | - | 100.75 | - | 96.84 | 0.610 | 0.206 |
| SE | 4.31 | - | 4.47 | - | 4.71 | - | 4.50 | ||||
| LZ (n = 29) | Mean | 102.58 | - | 96.59 | - | 102.91 | - | 106.48 | 0.292 | ||
| SE | 4.65 | - | 4.44 | - | 4.85 | - | 5.01 | ||||
| PROMIS Sleep Disturbance | Placebo (n = 31) | Mean | 50.75 | 48.86 | 48.95 | 47.40 | 49.00 | 48.32 | 47.25 | 0.001 | 0.963 |
| SE | 1.46 | 1.41 | 1.44 | 1.40 | 1.44 | 1.42 | 1.39 | ||||
| LZ (n = 29) | Mean | 50.43 | 49.71 | 49.64 | 48.23 | 50.01 | 49.69 | 48.32 | 0.060 | ||
| SE | 1.46 | 1.45 | 1.45 | 1.43 | 1.50 | 1.49 | 1.45 | ||||
| PROMIS Sleep-Related Impairment | Placebo (n = 31) | Mean | 50.59 | 48.28 | 47.76 | 46.46 | 48.73 | 48.11 | 47.13 | 0.005 | 0.730 |
| SE | 1.62 | 1.54 | 1.56 | 1.52 | 1.60 | 1.58 | 1.54 | ||||
| LZ (n = 29) | Mean | 50.98 | 51.18 | 49.08 | 47.98 | 49.32 | 48.70 | 47.19 | 0.003 | ||
| SE | 1.64 | 1.66 | 1.60 | 1.59 | 1.64 | 1.62 | 1.57 |
| AE Class | Diagnosis or symptom | Placebo (N=35) | LZ (N=35) |
|---|---|---|---|
| Muscular | n | 1 (2.9%) | 0 (0%) |
| Sore joints | 1 (2.9%) | 0 (0%) | |
| Gastrointestinal | n | 1 (2.9%) | 1 (2.9%) |
| Stomach pain/ bloating | 1 (2.9%) | 1 (2.9%) | |
| Sleep | n | 2 (5.7%) | 0 (0%) |
| Worsened sleep | 2 (5.7%) | 0 (0%) | |
| Dermatological | n | 2 (5.7%) | 0 (0%) |
| Swollen lips | 1 (2.9%) | 0 (0%) | |
| Face rash | 1 (2.9%) | 0 (0%) | |
| Ocular | n | 1 (2.9%) | 2 (5.7%) |
| Sore eyes/ eye irritation | 1 (2.9%) | 2 (5.7%) | |
| All Adverse events | n | 7 (20.0%) | 3 (8.6%) |
| Number of participants experiencing treatment-related AE* | n | 5 (14.3%) | 3 (8.6%) |
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