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    Features

    Nutraceuticals for Healthy and Restful Sleep

    GABA, Apocynum venetum, and glycine have different mechanisms of action, which is important when creating a formula that addresses multiple sleep issues.

    Nutraceuticals for Healthy and Restful Sleep
    By Gene Bruno, MS, MHS, RH(AHG), VP, Scientific and Regulatory Affairs, NutraScience Labs09.20.22
    Difficulty getting to sleep or staying asleep is a relatively common problem. According to population-based studies and other research around the world, about 30% of adults report one or more insomnia symptoms.1,2 Likewise, a U.S. survey reported that about 20% or more of older American adults use some form of sleep aid, including prescription or over-the-counter drugs or alcohol.3

    Unfortunately, many sleep-inducing medications are associated with side effects, including daytime sleepiness, dry mouth, and blurred vision—and most, but not all, are not recommended for more than a few weeks.4,5 Not surprisingly, this leaves the door wide open for natural sleep-support alternatives.

    Common Sleep Alternatives

    Two of the most common natural sleep alternatives include melatonin and valerian root—both of which have solid research to support their efficacy. However, both may have side effects in some people.

    For example, the most common side effects of melatonin include daytime drowsiness, headache, and dizziness—although these don't seem to occur any more frequently than with placebo.6 Likewise, valerian side effects reported in clinical studies include headache, gastrointestinal upset, mental dullness, excitability, uneasiness, and cardiac disturbances.7,8

    So what other options are there? As it turns out, quite a few. In this article, I’m going to focus on three of my favorites: GABA, Apocynum venetum, and glycine. These nutraceuticals have different mechanisms of action, which is important when creating a sleep formula.

    GABA and Apocynum venetum

    The primary neurotransmitter in the central nervous system for exerting sedative and anti-anxiety effects is gamma amino butyric acid (GABA).9 Known for its long history of use in Traditional Chinese Medicine, Apocynum venetum is an herbal remedy with efficacy for soothing the nerves, insomnia, and for other purposes.10 Individually and together, human clinical research has shown that these two nutraceuticals have meaningful stress-reducing, mood-enhancing, and sleep-promoting effects.

    For example, in one single-blind, placebo-controlled study, an EEG test demonstrated that 100 mg/day GABA and 25 mg/day Apocynum venetum leaf extract had beneficial effects on sleep.11 Specifically, GABA shortened the time it took to fall asleep, and increased non-rapid eye movement (REM) sleep time, while Apocynum venetum leaf extract induced deep sleep, and they functioned complementarily with simultaneous intake.

    The researchers concluded that this combination can be regarded as safe and appropriate for daily intake in order to improve the quality of sleep.

    Other studies showed that GABA works effectively as a natural relaxant, inducing relaxation, diminishing anxiety, and reducing stress.12,13 Likewise, studies on Apocynum venetum leaf extract significantly improved anxiety and reduced insomnia in the middle of the night as well as later in the sleep cycle.14,15

    Glycine

    Glycine is a non-essential amino acid with indispensable roles in brain chemistry. To understand glycine’s contribution to sleep, you must first understand that, while you're sleeping, body temperature can be 1 to 2 degrees lower than in the daytime. Body temperature starts to fall as bedtime approaches, paving the way for a good night's sleep.16

    Conversely, a warmer environment and subsequent body temperature increases wakefulness and decreases slow wave sleep and rapid eye movement sleep.17 When ingested before bedtime, glycine has been shown to significantly improve subjective sleep quality issues in individuals suffering from insomnia by decreasing core body temperature and maintaining this decrease during sleep.18

    In a randomized, single-blind, crossover trial, human volunteers who have been continuously experiencing unsatisfactory sleep, ingested 3 g of glycine or placebo before bedtime.19 Subjective sleep quality and changes in polysomnography (PSG)—a comprehensive test that records brain waves, blood oxygen levels, heart rate and breathing, and eye and leg movements—during sleep were analyzed. Effects on daytime sleepiness and daytime cognitive function were also evaluated.

    Results demonstrated that glycine improved subjective sleep quality and sleep efficiency (sleep time/in-bed time), and shortened PSG latency both to sleep onset and to slow wave sleep without changes in the sleep architecture. Glycine lessened daytime sleepiness and improved performance of memory recognition tasks.

    In conclusion, glycine supplementation before bedtime produces subjective and objective improvement in sleep quality in a different way than traditional hypnotic drugs such as benzodiazepines.

    Likewise, in another randomized, double-blind, crossover trial, volunteers with complaints about sleep quality ingested 3 g of glycine or placebo before bedtime.20 The results showed that glycine supplementation significantly improved fatigue, “liveliness and peppiness,” and clear headedness.

    Also, a randomized, single-blind, crossover trial was conducted to evaluate the effects of 3 g of glycine or placebo taken before bedtime on daytime sleepiness, fatigue, and performance in sleep-restricted healthy subjects.21 Results found that, in subjects given glycine, there was a significant reduction in fatigue and a tendency toward reduced sleepiness, as well as a significant improvement in psychomotor vigilance test.

    Conclusion

    Difficulty getting to sleep and/or staying asleep is common. While there are certainly many well-researched nutraceuticals that can help, studies show that GABA, Apocynum venetum, and glycine are very good choices.

    These nutraceuticals have different mechanisms of action, which is important when creating a sleep formula in order to approach the problem from different angles.

    About the Author: Gene Bruno, MS, MHS, RH (AHG) is a certified nutritionist and registered herbalist with 42 years of dietary supplement industry experience. He currently serves as both the vice president of scientific and regulatory affairs at NutraScience Labs and professor of nutraceutical science at Huntington University of Health Sciences.

    References

    1. Ancoli-Israel, S., Roth, T. (1999). Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep. 1999;22(Suppl 2):S347–53. https://pubmed.ncbi.nlm.nih.gov/10394606/
    2. Morin, C. et al. (2006). Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med. 2006;7(2):123-30. https://pubmed.ncbi.nlm.nih.gov/16459140/
    3. Johnson, E. et al. (1998). Epidemiology of alcohol and medication as aids to sleep in early adulthood. Sleep. 1998 Mar 15;21(2):178-86. https://pubmed.ncbi.nlm.nih.gov/9542801/
    4. PubMed Health: Insomnia. National Center for Biotechnology Information, U.S. National Library of Medicine Bethesda MD.
    5. Insomnia: Treatment & Drugs. Mayo Foundation for Medical Education and Research. Jan. 7, 2011. Retrieved December 2, 2011 from https://www.mayoclinic.org/diseases-conditions/insomnia/symptoms-causes/syc-20355167
    6. Buscemi, N. et al. Melatonin for treatment of sleep disorders. Summary, Evidence Report/Technology Assessment #108. (Prepared by the Univ of Alberta Evidence-based Practice Center, under Contract#290-02-0023.) AHRQ Publ #05-E002-2. Rockville, MD: Agency for Healthcare Research & Quality. November 2004. https://www.ncbi.nlm.nih.gov/books/NBK11941/
    7. Klepser, T. et al. (1999). Unsafe and potentially safe herbal therapies. Am J Health Syst Pharm 1999;56:125-38. https://pubmed.ncbi.nlm.nih.gov/10030529/
    8. National Toxicology Program, US Department of Health and Human Services. Chemical Information Review Document for Valerian (Valeriana officinalis L.) [CAS No. 8057-49-6] and Oils [CAS No. 8008-88-6]. Supporting Nomination for Toxicological Evaluation by the National Toxicology Program. November 2009. https://ntp.niehs.nih.gov/ntp/noms/support_docs/valerian_nov2009_508.pdf
    9. Kalant, H. et al. (1998). Principles of Med. Pharmacology. New York, NY: Oxford Univ Press, 1998.
    10. Xie, W. et al. (2012). Botany, traditional uses, phytochemistry and pharmacology of Apocynum venetum L. (Luobuma): A review. J Ethnopharmacol. 2012 May 7;141(1):1-8. https://pubmed.ncbi.nlm.nih.gov/22421379/
    11. Yamatsu, A. et al. (2015). The Improvement of Sleep by Oral Intake of GABA and Apocynum venetum Leaf Extract. J Nutr Sci Vitaminol (Tokyo). 2015;61(2):182-7. https://pubmed.ncbi.nlm.nih.gov/26052150/
    12. Abdou, A. et al. (2006). Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201-8. https://pubmed.ncbi.nlm.nih.gov/16971751/
    13. Nakamura, H. et al. (2009). Psychological stress-reducing effect of chocolate enriched with gamma-aminobutyric acid (GABA) in humans: assessment of stress using heart rate variability and salivary chromogranin A. Int J Food Sci Nutr. 2009;60 Suppl 5:106-13. https://pubmed.ncbi.nlm.nih.gov/19462324/
    14. Venetron® brochure, Tokiwa. Summarized in Maypro document “Venetron Clinical Evidence.” Topic: What was the effect of a daily dose of 50 mg of Venetron® in individuals with mild depression over 8 weeks? https://humanclinicals.org/project/venetron/
    15. Venetron® brochure, Tokiwa. Summarized in Maypro document “Venetron Clinical Evidence.” Topic: What have been the results of Venetron® in case studies of patients having depression, PMS, anxiety, and/or insomnia? https://humanclinicals.org/project/venetron/
    16. What Happens to Your Body When You Sleep? WebMD. Medically Reviewed by Nayana Ambardekar, MD on March 13, 2021. Retrieved September 12, 2022 from https://www.webmd.com/sleep-disorders/what-happens-body-during-sleep#:~:text=you're%20in.-,Body%20Temperature,for%20a%20good%20night's%20sleep.
    17. Okamoto-Mizuno, K., Mizuno, K. (2012). Effects of thermal environment on sleep and circadian rhythm. J Physiol Anthropol. 2012; 31(1): 14. https://pubmed.ncbi.nlm.nih.gov/22738673/
    18. Bannai, M., Kawai, N. (2012). New Therapeutic Strategy for Amino Acid Medicine: Glycine Improves the Quality of Sleep. J Pharmacol Sci. 2012; 118: 145 – 148. https://pubmed.ncbi.nlm.nih.gov/22293292/
    19. Yamadera, W. et al. (2007). Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological Rhythms. 2007; 5: 126–131. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1479-8425.2007.00262.x
    20. Inagawa, K. et al. (2006). Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep and Biological Rhythms. 2006; 4(1): 75-77. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1479-8425.2006.00193.x
    21. Mannai, M. et al. (2012). The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Front Neurol. 2012 Apr 18; 3:61. https://pubmed.ncbi.nlm.nih.gov/22529837/
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