Natural Sleep Aids Products

Natural Sleep Aids Products
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Natural Sleep Aids Products

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We are a big fan of good sleep. “There isn’t really any aspect of your health, mind, or wellness that isn’t dependent on sufficient sleep.”Matthew Walker says. Therefore, we are happy to come up with the solution for restful sleep and overall wellbeing. In the attached 6.5 pages’ content, you will discover 10 natural sleep aids, including specifications, clinical trials, applications, regulatory info and commercial cases.
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Sleep isn’t a luxury. It’s a non-negotiable human necessity
- sleep smarter for overall well-being


World Health Organization has pointed out that roughly two-thirds of adults sleep less than 8 h per night, which leads to a silent global epidemic of sleep deprivation.[1] Besides, sleep disorder is alarmingly prevalent. One study investigated in the Netherlands reported 21.2% of the males and 33.2% of the females had some type of sleep disorder. [2]

Society, however, has undervalued even neglected the importance of sleep for far too long. And current economical development exploits our demanding work schedule, which leads to the always-on culture squeezing our biological necessity, sleep. 

In fact, sufficient sleep can help to prevent all health problems, such as poor memory, lack of concentration, low mood, and the risk for depression, obesity, type 2 diabetes, heart disease and high blood pressure. [3] Having good sleep is almost like a life-support system. It’s the elixir of life. In the long run, it is an investment in health-span; in the short run, it’s a guarantee of a functional state for the productivity of tomorrow. In addition, when you sleep (and dream) better, you are better at 
processing information and coming up with creative ideas.[4] It is an undervalued recovery tool for high performance.[5]

 

Product name

Botanical/Latin name

Specification

Test method

Part used

Valerian Extract

Valeriana officinalis

4:1

TLC

Root

Passionflower Extract

Passiflora incarnate L

Flavones 5%

UV

Aerial parts

Lavender Extract

Lavandula angustifolia

4:1

TLC

Aerial parts

L-Theanine

Camellia sinensis (L.)

40%

HPLC

Leaf

5-HTP

Griffonia Simplicifolia

40%

HPLC

Seed

Hops Extract

Humulus lupulus L

Flavones 5%

UV

Flower

Lemon Balm Extract

Melissa Officinalis.

Flavones 5%

UV

Root

Product name

Specification

Test method

CAS NO.

Melatonin

98.5%~101.5%

USP40

73-31-4

Magnesium(Magnesium citrate anhydrous)

Mg 15%-16%

EP

144-23-0

Magnesium(Magnesium citrate tribasic nonahydrate)

Mg 10.3%-12.1%

EP

153531-96-5

Magnesium(Magnesium glycinate anhydrous)

≥Mg 14.0%

Enterprise

standard

14783-68-7

L-Tryptophan

98.5~101.5%

Titration

73-22-3

Note:

1) Country of origin: China. All the raw materials of these botanicals are cultivated in China. The full supply chain of all theabove-mentioned ingredients is covered in China. 
2) Other grades might be available after consultation. Third-party test reports are possible upon your request. 
3) Standard packaging is 25kg/drum and shelf-life is 24 months.
4) L-Theanine has another source(i.e., 98.0% ~102.0%, HPLC) that originates from L-Pyroglutamic acid.

For some people who are taking sleep medication, it’s worth mentioning that the side effects might be concerning, including addiction, and reduced emotional and cognitive function with long-term use. [6][7] In comparison, natural sleep aids have shown beneficial effects and tend to have no or minimal side effects. They are also much less likely to cause dependence. 

While before taking any sleep-promoting supplement, we would suggest you optimize sleep hygiene and your sleep habits first(e.g., Matthew Walker is one of the world-leading sleep researchers).

Applications:
 
Note:

1) Free samples of the above-mentioned ingredients are available upon your request. 
2) According to EFSA, an AI(adequate intake) for magnesium is set at 350 mg/day for adult men and 300 mg/day for adult women. For children aged 1 to < 3 years, an AI for magnesium is set at 170 mg/day for both sexes. [8]While please check and follow the local regulation of the targeted country. In UK, L-Tryptophan has a maximum daily dose of 220 mg. [9] For other above-mentioned ingredients, there is no established RDI at this moment.
3) For melatonin, 0.5 milligrams up to 2 milligrams is the most recommended dose in the medical community(0.5–5 mg per day 
have been used in human clinical studies). [10][11]

Monographs:
 

Valerian (Valeriana officinalis) belonging to valerianaceae family is a well-known medicinal plant for its benefit of sleep aid and sedative, as well as relaxing smooth muscle. It’s widely used all over the world, especially in Europe, China and Middle East. [12]

More than 150 chemical constituents were found in valerian of which many are physiologically active. The pharmacologically active compounds found in valerian extract are alkaloids, terpenes, organic acids and its derivatives, valepotriates and flavones. [12]

Selected research studies: Effect of valerian on sleep quality in postmenopausal women: a randomized placebo-controlled clinical trial (Taavoni et.al.2011) [13]

100 postmenopausal women participated in the study for 4 weeks. They were treated with a daily administration of 530 mg of concentrated valerian extract. Valerian significantly improves the quality of sleep among postmenopausal women who are experiencing insomnia.Tolerability and efficacy of valerian/lemon balm in healthy volunteers (a double-blind, placebo-controlled, multicentre study)(Cerny et.al. 1999) [14]

98 healthy volunteers went through a 30 days treatment with one group received 360 mg valerian and 240 mg lemon balm. The group taken valerian/lemon balm revealed a significantly higher quality of sleep.

Passionflower (Passiflora incarnata L.) is used in phytotherapy as a mild sedative and anxiolytic agent. This species is native to the South-Eastern United States, but it is also cultivated in Europe, Asia and Australia. [15]

The primary constituents of Passiflora are flavonoids, maltol, cyanogenic glycosides and indole alkaloids. [16][17][18][19]

Selected research studies: A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (Passionflower) herbal tea on subjective sleep quality (Ngan et.al.2011) [20]

41 participants consumed a cup of tea and filled out a sleep diary for 7 days. The findings suggest that the consumption of a low dose of Passiflora incarnata, in the form of tea, has short-term subjective sleep benefits for healthy adults with mild fluctuations in sleep quality.

Effects of Passiflora incarnata Linnaeus on polysomnographic sleep parameters in subjects with insomnia disorder: a doubleblind randomized placebo-controlled study (Lee et.al. 2020) [21]
110 adult participants with insomnia disorder received either 60 mg of Passionflower extract or the placebo daily for 2 weeks. Total sleep time was significantly increased in the Passionflower group compared with the placebo group.

Lavender (Lavandula angustifolia), in a form of essential oil, is widely used in aromatherapy for its documented sedative and hypnotic properties. [22] Lavender is native to the Western European part of the Mediterranean region. [23]

The key active components are found to be linalyl acetate and linalool which occur in varying amounts depending on species. [24]

Selected research studies: The effect of lavender aromatherapy on autonomic nervous system in midlife women with insomnia. Evidence-based complementary and alternative medicine (Chien et.al.2012) [25]

67 women with Insomnia underwent a 12 weeks of lavender aromatherapy(totally received 24 times of lavender inhalation). Women who received aromatherapy experienced a significant improvement in sleep quality after the intervention.

Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of ‘subsyndromal’ anxiety disorder: a randomized, double-blind, placebo-controlled trial (Kasper et.al. 2010) [26]

221 people with anxiety disorder were orally administered 80mg lavender oil supplement or a placebo per day. By the end of the 10-week study, the supplementation of lavender oil showed significant benefits on the quality and duration of sleep, as well as improvement in general mental and physical health.

L-Theanine, an amino acid naturally found abundant in tea leaves, has anxiolytic effects via the induction of brain waves. It will not cause additive and other side effects associated with conventional sleep inducers. [27]

In healthy humans, L-theanine is also reported to have positive effects on improving cognitive functions( e.g., attention and memory) and antipsychotic therapy in patients with schizophrenia and schizoaffective disorder.[28][29]

Selected research studies: The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial (Lyon et.al. 2011) [30]

98 male children consumed L-theanine 400 mg or placebo daily for a period of six-week treatment. L-theanine supplementation resulted in higher sleep percentage and sleep efficiency scores, along with a non-significant trend for less activity during sleep.

Effects of L-theanine administration on stress-related symptoms and cognitive functions in healthy adults: a randomized controlled trial (Hidese et.al. 2019) [31]

30 health individuals were blindly assigned for four-week administration of L-theanine (200 mg/day) or placebo tablets daily. L-theanine administration demonstrated a beneficial effect on the alleviation of sleep quality problems (e.g., disturbances in sleep latency, use of sleep medication).

5-Hydroxytryptophan (5-HTP) is an aromatic amino acid naturally produced by the body. Commercially, it is produced by extraction from the seeds of the African plant, Griffonia simplicifolia. [32]

5-HTP is shown to increase the production of serotonin in the brain, which may further regulate sleep, depression, anxiety, aggression, appetite, temperature, sexual behavior, and pain sensation.[32]

Selected research studies: L-5-Hydroxytryptophan treatment of sleep terrors in children (Bruni et.al. 2004) [33]

45 children affected by sleep terrors participated in the study and 31 randomly selected patients were administrated with 2 mg/kg of 5-HTP per day for 6 months. The results confirmed that 5-HTP treatment enables a long-term improvement of sleep terrors.

Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome (Caruso et.al. 1990) [34]

50 patients with primary fibromyalgia syndrome received oral administration of 100 mg 5-HTP or placebo three times a day for 30 days. Significant improvements were seen in areas like tender points, subjective pain severity, morning stiffness, sleep patterns, anxiety ratings, and fatigue ratings.

Hops are widely used as a major ingredient for brewing beer and they exhibit sedative and hypnotic properties. Hop is native to temperate regions of the Northern Hemisphere. [35]

The main constitutes of hops are alpha acids(Humulones), beta acids(Lupulone, Colupulone) and 4-Desoxyhumulone. The therapeutic properties may attribute to alpha acids.[36]

Selected research studies: Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial (Morin et.al. 2005) [37]

A total of 184 adults with insomnia were given a combination of 187 mg valerian and 41.9mg hops or placebo per day for 28 days. The findings showed that the valerian-hops combination has a modest hypnotic effect, which indicates that valerian-hops combination might be useful to treat mild insomnia.

Sleep improving effects of a single dose administration of a valerian/hops fluid extract. A double blind, randomized, placebocontrolled sleep-EEG study in a parallel design using the electrohypnogram (Dimpfel et.al. 2008) [38]
44 poor sleepers took a single dose of diluted valerian/hops fluid extract or placebo. The study has shown evidence for a positive effect of a combined valerian/hops fluid extract on sleep quality.

Lemon balm is widely cultivated in Europe and North America. It has therapeutic properties, such as antioxidant, anti-inflammatory, antimicrobial and antidepressant properties, as well as a wide range of applications in the treatment of sleep disorders, neurodegenerative diseases and obesity, etc. [39]

Lemon balm contains phenolic compounds, L-ascorbic acid, carotenoids, flavonoids and terpenoids. Lemon balm leaves are rich in flavonoids (0.5 % dry weight) consist of quercitrin (a derivative of quercetin), ramnocitrin, luteolin and its derivatives.[39]

Selected research studies: Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances (Cases et.al. 2011) [40]

20 stressed volunteers were treated with a daily administration of lemon balm extract(standardized to more than 7% rosmarinic acid and greater than 15% hydroxycinnamic acid derivatives) for 15 days. The result demonstrates the positive effects of lemon balm extract on easing insomnia and relieving stress-related symptoms.

A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children.(Müller et.al. 2006[41]

918 children were treated with a maximum of 640 mg valerian root dry and 320 mg lemon balm leaf dry extract daily for at least 4 weeks. the treatment was found very effective in treating restlessness and dyssomnia among young children.

Melatonin is a hormone that your body produces naturally, and it signals to your brain that it’s time to sleep. Melatonin can be efficacious in helping you with the timing of your sleep, especially under conditions of jetlag. [42]

Melatonin has been used for the last three decades for the treatment of sleep disorders in adults and children. [43] In contrast to most sleep medications, melatonin has little dependence potential and is not associated with habituation, neither hangover. [44]

Selected research studies: Meta-analysis: melatonin for the treatment of primary sleep disorders (Ferracioli-Oda et.al., 2013) [44]
19 studies involving 1683 subjects were included in this meta-analysis. Melatonin demonstrates significant efficacy in reducing sleep onset latency, increasing total sleep time and improving overall sleep quality. The effects of melatonin on sleep are modest but do not appear to dissipate with continued melatonin use.

Prolonged-release melatonin for insomnia–an open-label long-term study of efficacy, safety, and withdrawal (Lemoine et.al. 2011) [45]
244 adults with primary insomnia were given 2 mg prolonged-release melatonin or placebo daily for 12 months of treatment. The sleep quality has increased in the group that consumed melatonin. There were no adverse events(e.g., withdrawal symptom, suppression of endogenous) reported in the study.

Magnesium is involved in 300 biochemical reactions in the body. [46] It is an essential cofactor for many enzymatic reactions, especially energy metabolism and neurotransmitter synthesis.[47]

Magnesium (Mg) supplementation is often reported to improve sleep. However, the biological mechanisms linking magnesium to sleep are not well understood.[46]

Selected research studies: The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebocontrolled clinical trial (Abbasi et.al. 2012) [48]

46 elderly received 500 mg magnesium or placebo daily for 8 weeks. Supplementation of magnesium appears to improve subjective measures of insomnia such as sleep efficiency, sleep time and sleep onset latency, early morning awakening.

Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis (Mah et.al. 2021) [49]
Three randomized control trials (RCT) were included comparing oral magnesium to placebo among 151 older adults in three countries. The evidence may support oral magnesium supplements (less than 1 g quantities given up to three times a day) for improved sleep parameters(i.e., treating insomnia symptoms). 

L-tryptophan is an essential amino acid that humans need to obtain from the diet(i.e., protein-rich food and supplementation). [50]

Tryptophan is the unique precursor for the biosynthesis of serotonin and melatonin which both play key roles in regulating the sleep-wake cycle. [51][52] Consumption of foods that are high in L-tryptophan, such as milk, is linked to improved sleep outcomes. [53][54]

Selected research studies: Tryptophan-enriched cereal intake improves nocturnal sleep, melatonin, serotonin, and total antioxidant capacity levels and mood in elderly humans.(Bravo et.al. 2013) [55]
35 middle-aged/elderly volunteers consumed standard cereals (22.5 mg tryptophan in 30 g cereals per dose) at control week and cereals enriched with a higher dose of tryptophan (60 mg tryptophan in 30 g cereals per dose) at treatment week. The consumption of cereals containing the higher dose of tryptophan increased sleep efficiency, actual sleep time, immobile time, and decreased total nocturnal activity, sleep fragmentation index, and sleep latency.

Impact of experimentally induced serotonin deficiency by tryptophan depletion on sleep EEC in healthy subjects. (Voderholzeret.al. 1998) [56] 

A total of 12 healthy subjects were given specific diets to control tryptophan intake for 4 consecutive nights. After being tryptophan depleted, the subjects were shown decreased non-rapid eye movement, an increase of wake %, and of rapid eye movement (REM) density compared with baseline.


Commercial examples:

Feel Sleep (£24.29/Box)

Brand: Feel

Serving size 5g | Serving per container 30(150g)

Nutritional Information

Per serve

% NRV

L-Glycine

3,700 mg

 

Magnesium (as Bisglycinate

200 mg

53%

L-Tryptophan

150 mg

-

Rhodiola Extract 4:1 (Rhodiola rosea, standardised to

contain 3% Rosavins and 1% Salidrosides)

100 mg

-

Passionflower Extract 4:1 (Passiflora incarnata)

100 mg

-

Lemon balm Extract 4:1 (Melissa officinalis)

100 mg

-

California poppy (Eschscholzia californica)

100 mg

-

Hops Extract 4:1 (Humuluslupulus)

100 mg

-

Chromium (as Picolinate)

100 mg

-

- NRV not established

50mcg

125%

 

Sleep & Relax™ ($29.99/Bottle)

Brand: Gaia herbs

Serving size 2 capsules | Serving per container 25

Nutritional Information

Per serve

% NRV

Organic Passionflower leaf freeze-dried extract

387 mg

-

Organic Valerian root

203 mg

-

Organic Valerian root freeze-dried extract

87 mg

-

Proprietary Blend

290 mg

-

Organic Lemon Balm leaf, Organic Lemon Balm leaf freeze-dried extract, Organic

California Poppy aerial parts, Organic California Poppy aerial parts freeze-dried

extract, English Lavender flower essential oil, Sweet Marjoram aerial parts essential oil

- NRV not established


Sleep3 Tri-Layer Melatonin ($19.99/Box)

Brand: NATURE'S BOUNTY

Serving size 1 tablet | Serving per container 60

Nutritional Information

Per serve

% NRV

L-Theanine

200 mg

-

Nighttime Herbal Blend

50 mg

-

Chamomile Extract(Matricaria recutita)(flower), Lavender Extract (Lavandula

officinalis)(aerial), Lemon Balm Extract (Melissa officinalis)(leaf), Valerian Root

Extract(Valeriana officinalis)(root)

Melatonin

10 mg

-

- NRV not established

Regulation:

Novel food status: 
- All the above-mentioned ingredients are non-novel food in Europe. L-Theanine extracted and isolated from green tea(Camellia sinensis) is not novel only in food supplements. L-Theanine from other sources is novel food. The seeds of Griffonia simplicifolia are considered not novel in food supplements. [57][58] 
• EFSA authorized health claims:
- Melatonin: 1)contributes to the alleviation of subjective feelings of jet lag. 2) contributes to the reduction of timetaken to fall asleep. [59] 
- Magnesium: 1)contributes to a reduction of tiredness and fatigue. 2)contributes to electrolyte balance. 3) contributesto normal energy yielding metabolism. 4) contributes to normal functioning of the nervous system. 5) contributes to normal muscle function. 6) contributes to normal protein synthesis. 7) contributes to normal psychological function. 8) contributes to the maintenance of normal bones. 9) contributes to the maintenance of normal teeth. 10) has a role in the process of cell division. [59]
- A few health claims of the above-mentioned ingredients were summited and recorded in the file of consolidated list of Article 13 health claims List of references received by EFSA.[60]

Regulation:
[1] Lyon, L. (2019). Is an epidemic of sleeplessness increasing the incidence of Alzheimer’s disease?. Brain, 142(6), e30-e30.
[2] Nielen M.M.J., Spronk I., Davids R., Zwaanswijk M., Verheij R.A., Korevaar J.C. Incidentie en Prevalentie van Gezondheids Problemen in de 
Nederlandse Huisartsenpraktijk in 2012. NIVEL Zorgregistraties eerste lijn. [(accessed on 19 December 2018)]; Available 
online: https://www.nivel.nl/nl/nzr/zorgregistraties-eerstelijn.
[3] Natural Sleep Aids: Home Remedies to Help You Sleep. (n.d.). Johns Hopkins Medicine. 
https://www.hopkinsmedicine.org/health/wellness-and-prevention/natural-sleep-aids-home-remedies-to-help-you-sleep
[14]Sleep: The Overlooked Innovation Booster. (2021). Shleep. https://www.shleep.com/blog/sleep-the-overlooked-innovation-booster
[15]Sleep: The most overlooked and undervalued recovery tool for high performance. (2019). Medium. 
https://medium.com/@joshfaga/sleep-the-most-overlooked-and-undervalued-recovery-tool-for-high-performance-w-dr-steven-lockleyc7761f99f76c
[6]Why We Sleep: Unlocking the Power of Sleep and Dreams. (2017). Matthew Walker, Ph.D.
[7] Frase, L.; Nissen, C.; Riemann, D.; Spiegelhalder, K. Making sleep easier: Pharmacological interventions forinsomnia. Expert Opin. Pharmacother. 2018, 19, 1465–1473. [CrossRef]
[8] Scientific Opinion on Dietary Reference Values for magnesium1 EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). (2015).
[9]Risk assessment of “other substances” – L-tryptophan 
(https://vkm.no/download/18.645b840415d03a2fe8f2602c/1502802082645/Risk%20assessment%20of%20%22other%20substances%22%20%E2%80%93%20L-tryptophan.pdf). (2016).
[10] Ferracioli-Oda, E., Qawasmi, A., & Bloch, M. H. (2013). Meta-analysis: melatonin for the treatment of primary sleep disorders. PloSone, 8(5), e63773.
[11] European Commission. (2010). OPINION ON Melatonin - European Commission.
[12]Pilerood, S. A., & Prakash, J. (2013). Nutritional and medicinal properties of valerian (Valeriana officinalis) herb: A review. Int J Food Sci 
Nutr Diet, 1, 25-33.
[13]Taavoni, S., Ekbatani, N., Kashaniyan, M., & Haghani, H. (2011). Effect of valerian on sleep quality in postmenopausal women: a randomized placebo-controlled clinical trial. Menopause, 18(9), 951-955.
[14] Cerny, A., & Schmid, K. (1999). Tolerability and efficacy of valerian/lemon balm in healthy volunteers (a double-blind, placebocontrolled, multicentre study). Fitoterapia, 70(3), 221-228.
[15]Wohlmuth, H., Penman, K. G., Pearson, T., & Lehmann, R. P. (2010). Pharmacognosy and chemotypes of passionflower (Passiflora incarnata L.). Biological and Pharmaceutical bulletin, 33(6), 1015-1018.
[16]Poethke W, Schwarz C, Gerlach H. 1970. Components of Passiflora bryonioides. 2. Flavone derivatives. Planta Med 19: 177–188.
[17]Spencer KC, Seigler DS. 1984. Gynocardin from passiflora. Planta Med 50: 356–357.
[18]Marchart E, Krenn L, Kopp B. 2003. Quantification of the flavonoid glycosides in Passiflora incarnata by capillary electrophoresis. Planta Med 69: 452–456.
[19]Krenn L. 2006. Aktuelles über Passiflora incarnata. Z Phytother 27: 47–50.
[20]Ngan, A., & Conduit, R. (2011). A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (Passionflower) herbal tea on subjective sleep quality. Phytotherapy research, 25(8), 1153-1159.
[21]Lee, J., Jung, H. Y., Lee, S. I., Choi, J. H., & Kim, S. G. (2020). Effects of Passiflora incarnata Linnaeus on polysomnographic sleep parameters in subjects with insomnia disorder: a double-blind randomized placebo-controlled study. International clinical psychopharmacology, 35(1), 29-35.
[22]Bowles EJ. The Chemistry of Aromatherapeutic Oils. Third edition. Crowns Nest NSW, Australia: Allen & Unwin, 2003
[23]A Brief History On Our Love Of Lavender. (n.d.). High Country Gardens. https://www.highcountrygardens.com/gardening/lavenderhistory
[24] Cavanagh HM, Wilkinson JM. Biological activities of Lavender essential oil. Phytotherapy Research 2002;16:301–8.
[25]Chien, L. W., Cheng, S. L., & Liu, C. F. (2012). The effect of lavender aromatherapy on autonomic nervous system in midlife women with insomnia. Evidence-based complementary and alternative medicine, 2012.
[26]Kasper, S., Gastpar, M., Müller, W. E., Volz, H. P., Möller, H. J., Dienel, A., & Schläfke, S. (2010). Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of ‘subsyndromal’anxiety disorder: a randomized, double-blind, placebo-controlled trial. International clinical psychopharmacology, 25(5), 277-287.
[27]Rao, T. P., Ozeki, M., & Juneja, L. R. (2015). In search of a safe natural sleep aid. Journal of the American College of Nutrition, 34(5), 436-447.
[28]FOXE JJ, MORIE KP, LAUD PJ, ROWSON MJ, DE BRUIN EA, KELLY SP. Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task. Neuropharmacology 2012;62:2320–2327.
[29]RITSNER MS, MIODOWNIK C, RATNER Y et al. L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study. J Clin Psychiatry 2011;72:34–42.
[30]Lyon, M. R., Kapoor, M. P., & Juneja, L. R. (2011). The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Alternative medicine review, 16(4), 348.
[31]Hidese, S., Ogawa, S., Ota, M., Ishida, I., Yasukawa, Z., Ozeki, M., & Kunugi, H. (2019). Effects of L-theanine administration on stressrelated symptoms and cognitive functions in healthy adults: a randomized controlled trial. Nutrients, 11(10), 2362.

Regulation:
[32]Birdsall, T. C. (1998). 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Alternative medicine review: a journal of clinical therapeutic, 3(4), 271-280.
[33]Bruni, O., Ferri, R., Miano, S., & Verrillo, E. (2004). L-5-Hydroxytryptophan treatment of sleep terrors in children. European journal of pediatrics, 163(7), 402-407.
[34]Caruso, I., Puttini, P. S., Cazzola, M., & Azzolini, V. (1990). Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. Journal of international medical research, 18(3), 201-209.
[35]Benkherouf, A. Y., Eerola, K., Soini, S. L., & Uusi-Oukari, M. (2020). Humulone modulation of GABAA receptors and its role in hops sleeppromoting activity. Frontiers in neuroscience, 14, 1100.
[36]Stevens, R. (1967). The chemistry of hop constituents. Chemical Reviews, 67(1), 19-71.
[37]Morin, C. M., Koetter, U., Bastien, C., Ware, J. C., & Wooten, V. (2005). Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial. Sleep, 28(11), 1465-1471.
[38]Dimpfel, W., & Suter, A. A. (2008). Sleep improving effects of a single dose administration of a valerian/hops fluid extract. A double blind, randomized, placebo-controlled sleep-EEG study in a parallel design using the electrohypnogram. Zeitschrift für Phytotherapie, 29(S 1), P06.
[39] Świąder, K., Startek, K., & Wijaya, C. H. (2019). The therapeutic properties of Lemon balm (Melissa officinalis L.): Reviewing novel findings and medical indications. J. Appl. Bot. Food Qual, 92, 327-335.
[40]Cases, J., Ibarra, A., Feuillère, N., Roller, M., & Sukkar, S. G. (2011). Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Mediterranean journal of nutrition and metabolism, 4(3), 211-218.
[41]Müller, S. F., & Klement, S. (2006). A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine, 13(6), 383-387.
[42]Sleep Better With These Bedtime Rituals. (2020). Npr. https://www.npr.org/transcripts/705224709
[43]Claustrat B, Brun J, Chazot G (2005) The basic physiology and pathophysiology of melatonin. Sleep Med Rev 9: 11–24.
[44]Ferracioli-Oda, E., Qawasmi, A., & Bloch, M. H. (2013). Meta-analysis: melatonin for the treatment of primary sleep disorders. PloSone, 8(5), e63773.
[45]Lemoine, P., Garfinkel, D., Laudon, M., Nir, T., & Zisapel, N. (2011). Prolonged-release melatonin for insomnia–an open-label long-term study of efficacy, safety, and withdrawal. Therapeutics and clinical risk management, 7, 301.
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