• Chee Huei Phing Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, Malaysia
  • Ong Yong Chee Ministry of Health, Malaysia




Sleep disorder is common among the general population. A nutritional supplement containing alpha-s1-casein tryptic hydrolysate and L-theanine was evaluated for its effects in improving sleep quality. The study was conducted using a double-blind randomized trial.  Intervention group received once-daily capsules of 150 mg alpha s1 casein tryptic hydrolysate and 50 mg L-theanine, and the control group were given placebo (150 mg skimmed milk powder) for four weeks. The outcome measurements were assessed on weekly basis using PSQI, DASS-21, clinical and biochemical parameters. ANOVA test were used to assess within group differences and ANCOVA were used to check for differences between groups. Significantly lower (better) sleep latency score, sleep disturbances score and daytime dysfunction score were demonstrated on week-4 in intervention group compared to placebo group. Profound differences were observed between the two groups for anxiety and stress scores from week-3 onwards, in which lower anxiety and stress scores were observed in intervention group compared to placebo group. In addition, significantly lower depression score in intervention group compared to placebo group on week-4 was observed. Intervention supplement has demonstrated potent effects in relieving anxiety, stress, depression and sleep quality.


Dodge, R; Cline, MG; Quan, SF. The natural history of insomnia and its relationship to respiratory symptoms. Arch Intern Med 1995; 155: 1797-1800.

Ancoli-Israel, S; Roth, T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. Sleep 1999; 22(Suppl 2): S347-S353.

Bixler, EO; Vgontzas, AN; Lin HM; Vela-Bueno, A; Kales, A. Insomnia in central Pennsylvania. J Psychosom Res 2002; 53: 589-592.

Ohayon, MM; Guilleminault, C; Paiva, T; Priest, RG; Rapoport, DM; Sagales, T; Smirne, S; Zulley, J. An international study on sleep disorders in the general population: methodological aspects of the use of the Sleep-EVAL system. Sleep 1997; 20: 1086-1092.

Ohayon, MM; Caulet, M; Priest, RG; Guilleminault, C. DSM-IV and ICSD-90 insomnia symptoms and sleep dissatisfaction. Br J Psychiatry 1997; 171: 382-388.

Ohayon, MM; Caulet, M; Guilleminault, C. How a general population perceives its sleep and how this relates to the complaint of insomnia. Sleep 1997; 20: 715-723.

Roth, T; Ancoli-Israel, S. Daytime consequences and correlates of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. II. Sleep 1999; 22 (Suppl 2): S354-S358.

Thase, ME. Correlates and consequences of chronic insomnia. Gen Hospital Psychiatry 2005; 27: 100-12.

Perlis, ML; Giles, DE; Mendelson, WB; Bootzin, RR; Wyatt, JK. Psychophysiological insomnia: the behavioral model and a neurocognitive perspective. J Sleep Res 1997; 6: 179-188.

Sukegawa, T; Itoga, M; Seno, H; Miura, S; Inagaki, T; Salto, W; et al. Sleep disturbances and depression in the elderly in Japan. Psychiatry Clin Neurosci 2003; 57: 265-70.

Kaneita, Y; Uchiyama, M; Takemura, S; Yokoyama, E; Miyake, T; Harano, S; et al. Use of alcohol and hypnotic medication as aids to sleep among the Japanese general population. Sleep Med 2007; 8: 723-732.

Spiegel, K; Leproult, R; Van Cauter, E. Impact of sleep debt on metabolic and endocrine function. Lancet 1999; 4: 435-9.

Hayashino, Y; Fukuhara, S; Suzukamo, Y; Okamura, T; Tanaka, T; Ueshima, H. Relation between sleep quality and quantity, quality of life, and risk of developing diabetes in healthy workers in Japan: the High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study. BMC Public Health 2007; 7: 129.

Zailinawati, AH; Ariff KM; Nurjahan MI; Teng CL. Epidemiology of insomnia in Malaysian adults: A community-based survey in 4 urban areas. Asia Pacific Journal of Public health, 2008; 20(3): 2240-233.

Saverie, S; Wiliam, T; Francesc, XG; Margaret, T; Ngianga-Bakwin K. Sleep problems: An emerging global epidemic? Findings from the INDEPTH WHO-SAGE study among more than 40,000 older adults from 8 countries across Africa and Asia. Sleep 2012; 35(8): 1173-1181.

Benca, RM; Mood disorders. In: Kryger, T; Dement, WC; editors. Principles and practice of sleep medicine. 2000; Philadelphia: WB Saunders, pp. 1140-57.

De Saint Hilaire, Z; Straub, J; Pelissolo, A. Temperament and character in primary insomnia. Eur Psychiatry 2005; 20: 188-92.

Vollrath, M; Wicki, W; Angst, J. The Zurich study. VIII. Insomnia: association with depression, anxiety, somatic syndromes, and course of insomnia. Eur Arch Psychiatry Neurol Sci 1989; 239: 113-24.

Bonnet, MH; Arand, DL. Hyperarousal and insomnia. Sleep Med Rev 1997; 1: 97-108.

Hall, M; Buysse, DJ; Nowell, PD; Nofzinger, EA; Houck, P; Reynolds, CF; Kupfer, DJ. Symptoms of stress and depression as correlates of sleep in primary insomnia. Psychosom Med 2000; 62: 227-30.

Olajide, D; Lader, M. Depression following withdrawal from long term benzodiazepine use: a report of four cases. Psychol Med 1984; 14: 937-040.

Power, KG; Jerrom, DW; Simpson, RJ; Mitchell, M. Controlled study of withdrawal symptoms and rebound anxiety after six week course of diazepam for generalised anxiety. Br Med J (Clin Res Ed) 1985; 290: 1246-1248.

Rosenberg, HC; Chiu, TH. Time course for development of benzodiazepine tolerance and physical dependence. Neurosci Biobehav Rev 1985; 9: 123-31.

Staner, L; Ertlé, S; Boeijinga P; Rinaudo, G; Arnal, MA; Muzet, A; Lutringer, R. Next-day residual effects of hypnotics in DSM-IV primary insomnia: a driving simulator study with simultaneous electroencephalogram monitoring. Psychopharmacology (Berl) 2005; 181: 790-8.

Laird, DA; Drexel, H. Experimenting with food and sleep. I. Effects of varying types of foods in offsetting sleep disturbances caused by hunger pangs and gastric distress-children and adults. J Am Diet Assoc 1934; 10: 89-94.

Markus, CR; Jonkman, LM; Lammers, JH; Deutz, NE; Messer, MH; Rigtering, NE. Evening Intake of Lactalbumin May Improve Sleep and Morning Alertness. Am J Clin Nutr 2005; 81: 1026-33.27.

Semiz, M; Uslu, A; Korkmaz, S; Demir, S; Parlak, I; Sencan, M; Aydin, B; Uncu, T. Assessment of subjective sleep quality in iron deficiency anaemia. Afr. Health Sci 2015; 15(2): 621-627.

The Pittsburgh Sleep Quality Index (PSQI). Available from: http://www.sleep.pitt.edu/content.asp?id=1484&subid=2316.

Lovibond, PF; Lovibond, S. Manual for the Depression Anxiety Stress Scales. 1995; Sydney, Australia: School of Psychology, University of New South Wales.

Murphy, MH; Murtagh, EM; Boreham, CAG; Hare, LG; Nevill, AM. The effect of a worksite based walking programme on cardiovascular risk in previously sedentary civil servants. BMC Public Health 2006; 6(1): 136-143.

Musa, R; Fadzil, MA; Zain, Z. Translation, validation and psychometric properties of Bahasa Malaysia version of the Depression, Anxiety and Stress (DASS). ASEAN Journal of Psychiatry 2007; 8(2): 82-89.

Ariaratnam, S; Devi, A; Kaur, G; Sinniah, D; Suleiman, A; Thambu, M; et al. Psychiatric morbidity and survival in newly diagnosed treatment naïve cancer patients– A study from Malaysia. Biomed Res. 2008; 19(2): 113-116.

Altman, Douglas G. Practical statistic for medical research. Monographs on Statistics and Applied Probability (First Edition). 1991; Chapman and Hall.

Yamaada, T; Terashima, T; Okubo, T; Junela, LR; Yokogoshi, H. Effects of theanine, -glutamyethylamide, on neurotransmitter release and its relationship with glutamic acid neurotransmission. Nutr. Neurosci. 2005; 8: 219-226.

Kamath, AB; Wang, L., Das, H; Li, L; Reinhold, VN, Bukowski, JF. Antigens in tea-beverage prime human Vgamma 2v delta 2T cells in vitro and in vivo for memory and nonmemory antibacterial cytokine responses. Proc. Nat. Acad. Sci. USA 2003; 100: 6009.

Miclo, L; Perrin, E; Driou, A; Papadopoulous, V; Boujrad, N; Vanderesse, R; Boudler, JF; Desor D; Linden, G; Gallard, JL. Characterization of alpha-casozepine, a tryptic peptide from bovine alpha(s1)-casein with benzodiazepine-like activity. FASEB J 2001; 15(10): 1780-1782.

Berk, M; Dodd, S. Antidepressants and the placebo response. Hum Psychopharmacol 2005; 5: 305-307.

Mercier, JC; Grosclaude, F; Ribadeau-Dumas B. Primary structure of bovin alpha-s1-casein partial sequence. Eur J Biochem 1970; 16(3): 453-460.

Carmen, R.W., Van, V. Betsy L.M. (2007). Understanding power and rules of thumb for determining sample sizes. Tutorials in Quantitative Methods for Psychology; 3(2): 43-50.




How to Cite

Chee Huei Phing, & Ong Yong Chee. (2019). EFFECTS OF ALPHA-S1-CASEIN TRYPTIC HYDROLYSATE AND L-THEANINE ON SLEEP DISORDER AND PSYCHOLOGICAL COMPONENTS: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY. Malaysian Journal of Public Health Medicine, 19(1), 47–55. https://doi.org/10.37268/mjphm/vol.19/no.1/art.36