Nutr Res Pract.  2021 Jun;15(3):309-318. 10.4162/nrp.2021.15.3.309.

Effects of poly-gamma-glutamic acid and vitamin B 6 supplements on sleep status: a randomized intervention study

Affiliations
  • 1Department of Foods and Nutrition, College of Science and Technology, Kookmin University, Seoul 02707, Korea

Abstract

BACKGROUD/OBJECTIVES: Data regarding the effects of poly-γ-glutamic acid (γ-PGA) on sleep status are limited. This study aimed to test whether γ-PGA and vitamin B 6 (VitB6) supplements improve sleep duration and quality.
SUBJECTS/METHODS
A factorial randomized, double-blinded, placebo-controlled crossover study included 47 adults (25 men and 22 women) who were free of chronic disease. Stratified randomized allocation considered age and gender for three interventions, group A (supplementation with γ-PGA 600 mg; n = 16), group B (supplementation with VitB6 100 mg; n = 14), and group C (dual supplementation of both γ-PGA 600 mg and VitB6 100 mg; n = 17). Participants underwent a 1-mon intervention period, followed by a 1-mon washout period, and then a second 1-mon intervention period. Differences (mean ± SD) in nighttime sleep status before and after supplementation were compared between the placebo and intervention groups using nonparametric tests.
RESULTS
Significant changes in sleep duration (0.27 ± 0.98 h, P < 0.05) and the Pittsburgh Sleep Quality Index global score (−0.52 ± 1.58, P < 0.05) indicating improved sleep status were observed in the intervention compared with the placebo of group C while no significant changes were observed in groups A and B. No statistical significance was detected between the intervention and the placebo; however, there was a greater increase in the group C intervention (4.59 ± 38.5 ng/mL) in serum serotonin concentrations than the groups A and B interventions. No side effects were observed.
CONCLUSIONS
On the basis of these findings, the dual supplementation of γ-PGA and VitB6 may be effective as functional food components to improve nighttime sleep status. Trial Registration: Clinical Research Information Service Identifier: KCT0005083

Keyword

Functional food; vitamin B6; sleep

Figure

  • Fig. 1 Study flowchart.Group A received γ-PGA supplementation only; Group B received VitB6 supplementation only; Group C received both γ-PGA and VitB6 supplementation. The number of participants who were enrolled, dropped out, and completed the trial by interventions in the randomized, double-blinded, placebo-controlled, and crossover study.γ-PGA, poly-γ-glutamic acid; VitB6, vitamin B6.


Reference

1. King PW. Climbing Maslow's Pyramid. Introducing Abraham Maslow and His Pyramid. Kibworth Harcourt: Troubador Publishing Ltd.;2009. p. 3–21.
2. Park S, Cho MJ, Chang SM, Bae JN, Jeon HJ, Cho SJ, Kim BS, Chung IW, Ahn JH, Lee HW, Hong JP. Relationships of sleep duration with sociodemographic and health-related factors, psychiatric disorders and sleep disturbances in a community sample of Korean adults. J Sleep Res. 2010; 19:567–577. PMID: 20477953.
Article
3. Park SE, Kim HM, Kim DH, Kim J, Cha BS, Kim DJ. The association between sleep duration and general and abdominal obesity in Koreans: data from the Korean National Health and Nutrition Examination Survey, 2001 and 2005. Obesity (Silver Spring). 2009; 17:767–771. PMID: 19180067.
Article
4. Abrams RM. Sleep deprivation. Obstet Gynecol Clin North Am. 2015; 42:493–506. PMID: 26333639.
Article
5. Hwang SH, Kang JM, Seo JH, Han KD, Joo YH. Association between sleep duration and dizziness in Korean women: the Korea National Health and Nutrition Examination Survey. J Korean Med Sci. 2019; 34:e226. PMID: 31436054.
Article
6. Cunnington D, Junge MF, Fernando AT. Insomnia: prevalence, consequences and effective treatment. Med J Aust. 2013; 199:S36–40.
Article
7. Morin CM, Vallières A, Guay B, Ivers H, Savard J, Mérette C, Baillargeon L. Cognitive behavior therapy, singly and combined with medication, for persistent insomnia: acute and maintenance therapeutic effects. JAMA. 2011; 301:2005–2015.
8. Ebben M, Lequerica A, Spielman A. Effects of pyridoxine on dreaming: a preliminary study. Percept Mot Skills. 2002; 94:135–140. PMID: 11883552.
Article
9. Scholey A, Benson S, Gibbs A, Perry N, Sarris J, Murray G. Exploring the effect of lactium™ and Zizyphus complex on sleep quality: a double-blind, randomized placebo-controlled trial. Nutrients. 2017; 9:154.
Article
10. Lee H, Chang MJ, Kim SH. Effects of poly-γ-glutamic acid on serum and brain concentrations of glutamate and GABA in diet-induced obese rats. Nutr Res Pract. 2010; 4:23–29. PMID: 20198205.
Article
11. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989; 28:193–213. PMID: 2748771.
Article
12. Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep. 1991; 14:540–545. PMID: 1798888.
Article
13. Spira AP, Beaudreau SA, Stone KL, Kezirian EJ, Lui LY, Redline S, Ancoli-Israel S, Ensrud K, Stewart A. Osteoporotic Fractures in Men Study. Reliability and validity of the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale in older men. J Gerontol A Biol Sci Med Sci. 2012; 67:433–439. PMID: 21934125.
Article
14. Beaudreau SA, Spira AP, Stewart A, Kezirian EJ, Lui LY, Ensrud K, Redline S, Ancoli-Israel S, Stone KL. Study of Osteoporotic Fractures. Validation of the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale in older black and white women. Sleep Med. 2012; 13:36–42. PMID: 22033120.
Article
15. Sohn SI, Kim DH, Lee MY, Cho YW. The reliability and validity of the Korean version of the Pittsburgh Sleep Quality Index. Sleep Breath. 2012; 16:803–812. PMID: 21901299.
Article
16. Korean Nutrition Society. Ministry of Health and Welfare. Dietary Reference Intakes for Koreans. Seoul: Korean Nutrition Society;2015.
17. Ministry of Food and Drug Safety. Current Status of Functional Ingredients for Health Functional Food in Korea. Cheongju: Ministry of Food and Drug Safety;2016.
18. Kim TW, Lee TY, Bae HC, Hahm JH, Kim YH, Park C, Kang TH, Kim CJ, Sung MH, Poo H. Oral administration of high molecular mass poly-gamma-glutamate induces NK cell-mediated antitumor immunity. J Immunol. 2007; 179:775–780. PMID: 17617566.
19. Oyunbileg E, Jun N, Yoon D, Baik I. Effects of poly-gamma-glutamic acid on inflammatory and metabolic biomarkers in sleep-restricted rats. Sleep Biol Rhythms. 2018; 16:399–404.
Article
20. Luo Z, Guo Y, Liu J, Qiu H, Zhao M, Zou W, Li S. Microbial synthesis of poly-γ-glutamic acid: current progress, challenges, and future perspectives. Biotechnol Biofuels. 2016; 9:134. PMID: 27366207.
Article
21. Ito Y, Tanaka T, Ohmachi T, Asada Y. Glutamic acid independent production of poly (γ-glutamic acid) by Bacillus subtilis TAM-4. Biosci Biotechnol Biochem. 1996; 60:1239–1242.
22. Ogunleye A, Bhat A, Irorere VU, Hill D, Williams C, Radecka I. Poly-γ-glutamic acid: production, properties and applications. Microbiology (Reading). 2015; 161:1–17. PMID: 25288645.
Article
23. Park JH, Choi JC, Sung MH, Kang JH, Chang MJ. High molecular weight poly-gamma-glutamic acid regulates lipid metabolism in rats fed a high-fat diet and humans. J Microbiol Biotechnol. 2011; 21:766–775. PMID: 21791965.
Article
24. Tanimoto H, Fox T, Eagles J, Satoh H, Nozawa H, Okiyama A, Morinaga Y, Fairweather-Tait SJ. Acute effect of poly-gamma-glutamic acid on calcium absorption in post-menopausal women. J Am Coll Nutr. 2007; 26:645–649. PMID: 18187428.
25. Jun NR. Effect of poly-gamma glutamic acid, magnesium and vitamin B6 supplementation on metabolic and inflammatory biomarkers and sleep status in caffeine intake rat [dissertation]. Seoul: Kookmin University;2017.
26. Ciranna L. Serotonin as a modulator of glutamate- and GABA-mediated neurotransmission: implications in physiological functions and in pathology. Curr Neuropharmacol. 2006; 4:101–114. PMID: 18615128.
Article
27. Yin D, Dong H, Wang TX, Hu ZZ, Cheng NN, Qu WM, Huang ZL. Glutamate activates the histaminergic tuberomammillary nucleus and increases wakefulness in rats. Neuroscience. 2019; 413:86–98. PMID: 31202706.
Article
28. Lopez-Rodriguez F, Medina-Ceja L, Wilson CL, Jhung D, Morales-Villagran A. Changes in extracellular glutamate levels in rat orbitofrontal cortex during sleep and wakefulness. Arch Med Res. 2007; 38:52–55. PMID: 17174723.
Article
29. Messripour M, Mesripour A. Effects of vitamin B6 on age associated changes of rat brain glutamate decarboxylase activity. Afr J Pharm Pharmacol. 2011; 5:454–456.
30. Almeida MR, Mabasa L, Crane C, Park CS, Venâncio VP, Bianchi ML, Antunes LM. Maternal vitamin B6 deficient or supplemented diets on expression of genes related to GABAergic, serotonergic, or glutamatergic pathways in hippocampus of rat dams and their offspring. Mol Nutr Food Res. 2016; 60:1615–1624. PMID: 26935476.
31. Boonstra E, de Kleijn R, Colzato LS, Alkemade A, Forstmann BU, Nieuwenhuis S. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015; 6:1520. PMID: 26500584.
Article
32. Knudsen GM, Poulsen HE, Paulson OB. Blood-brain barrier permeability in galactosamine-induced hepatic encephalopathy. No evidence for increased GABA-transport. J Hepatol. 1988; 6:187–192. PMID: 3411098.
33. Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol. 2015; 7:a020412. PMID: 25561720.
Article
34. Mabunga DF, Gonzales EL, Kim HJ, Choung SY. Treatment of GABA from fermented rice germ ameliorates caffeine-induced sleep disturbance in mice. Biomol Ther (Seoul). 2015; 23:268–274. PMID: 25995826.
Article
35. Zhao W, Li Y, Ma W, Ge Y, Huang Y. A study on quality components and sleep-promoting effects of GABA black tea. Food Funct. 2015; 6:3393–3398. PMID: 26290415.
Article
36. Kim S, Jo K, Hong KB, Han SH, Suh HJ. GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. Pharm Biol. 2019; 57:65–73. PMID: 30707852.
Article
37. Hong KB, Park Y, Suh HJ. Sleep-promoting effects of a GABA/5-HTP mixture: Behavioral changes and neuromodulation in an invertebrate model. Life Sci. 2016; 150:42–49. PMID: 26921634.
Article
38. Jin HE, Choi JC, Lim YT, Sung MH. Prebiotic effects of poly-gamma-glutamate on bacterial flora in murine gut. J Microbiol Biotechnol. 2017; 27:412–415. PMID: 27974732.
Article
Full Text Links
  • NRP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr