Sleep Supplementation & Pharmacology — References

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Parent Topic: Sleep Supplementation & Pharmacology | References Hub: 01 - Foundations References MOC

Primary Literature & Landmark Studies

Citation: Hausenblas, H. A., Lynch, T., Hooper, S., Shrestha, A., Rosendale, D., & Gu, J. (2024). Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial. Sleep Medicine: X, 8, 100121.
Identifiers: DOI: 10.1016/j.sleepx.2024.100121 (DOI · SciDB · Scholar) | PMID: 39252819 (PubMed · Europe PMC)
Study Design: 21-day randomized, double-blind, placebo-controlled parallel trial in adults aged 35–55 with self-reported sleep problems ( $N = 80$ , combining subjective ISI/PROMIS scales with objective Oura Ring sleep tracking).
Key Quantitative Outcomes:
- Magnesium L-Threonate (1 g/day Magtein) significantly improved objective Deep Sleep scores ( $p = 0.008$ ) and REM Sleep scores ( $p = 0.028$ ) compared to placebo, alongside significant improvements in Insomnia Severity Index ( $p = 0.006$ ), daytime energy, and mental alertness.

Citation: Yamadera, W., Inagawa, K., Chiba, S., Bannai, M., Takahashi, M., & Nakayama, K. (2007). Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological Rhythms, 5(2), 126–131.
Identifiers: DOI: 10.1111/j.1479-8425.2007.00262.x (DOI · SciDB · Scholar) | Companion Mechanistic/Sleep Restriction Study: Bannai et al. (2012), Frontiers in Neurology, DOI: 10.3389/fneur.2012.00061 (DOI · SciDB · Scholar) (PMID: 22529837 (PubMed · Europe PMC))
Study Design: Randomized, single-blind, placebo-controlled crossover polysomnographic trial in humans experiencing unsatisfactory sleep ( $N = 11$ ).
Key Quantitative Outcomes:
- Ingestion of 3 g of glycine before bedtime significantly shortened latency to sleep onset ( $p = 0.014$ ) and latency to slow-wave sleep ( $p = 0.019$ ) while preserving physiological REM architecture and significantly reducing next-day daytime sleepiness and improving memory recognition performance.

Citation: Abbasi, B., Kimiagar, M., Sadeghniiat, K., Shirazi, M. M., Hedayati, M., & Rashidkhani, B. (2012). The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of Research in Medical Sciences, 17(12), 1161–1169.
Identifiers: PMID: 23853635 (PubMed · Europe PMC) | PMCID: PMC3703169 (PMC Full Text)
Study Design: 8-week randomized, double-blind, placebo-controlled trial in older adults with primary insomnia ( $N = 46$ ).
Key Quantitative Outcomes:
- Supplementation with 500 mg elemental magnesium daily significantly increased sleep time ( $p = 0.002$ ), sleep efficiency ( $p = 0.03$ ), serum renin ( $p < 0.001$ ), and serum melatonin ( $p = 0.007$ ), while significantly decreasing Insomnia Severity Index scores ( $p = 0.006$ ), sleep onset latency ( $p = 0.02$ ), and serum cortisol ( $p = 0.008$ ).

Citation: Mignot, E., Mayleben, D., Fietze, I., Leger, D., Zammit, G., Bassetti, C. L. A., Pain, S., Kohnen, R., & Dauvilliers, Y. (2022). Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. The Lancet Neurology, 21(2), 125–139.
Identifiers: DOI: 10.1016/S1474-4422(21)00436-1 (DOI · SciDB · Scholar) | PMID: 35065036 (PubMed · Europe PMC)
Study Design: Two multi-center, randomized, double-blind, placebo-controlled Phase 3 trials ( $N = 930$ in Trial 1; $N = 924$ in Trial 2) over 3 months.
Key Quantitative Outcomes:
- At month 3, daridorexant 50 mg significantly reduced Wake After Sleep Onset (WASO) by 22.8 minutes ( $p < 0.0001$ ) and Latency to Persistent Sleep (LPS) by 11.7 minutes ( $p < 0.0001$ ) vs. placebo, increased total sleep time by 19.8 minutes above placebo, improved IDSIQ daytime functioning scores, and maintained normal proportions of N1, N2, N3, and REM sleep without rebound insomnia or withdrawal.