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Known as the circadian rhythm, this internal body clock is on automatic repeat every 24 hours. It helps regulate our sleep and other functions such as our eating habits and body temperature.

The body clock resets everyday by using signals from external timekeepers, such as light and dark. The suprachiasmatic nucleus (SCN) of the hypothalamus, which directs the circadian program, has been called the brain’s “master clock”. Circadian timing, in which neurons fire in a 24-hour cycle, is organized in a hierarchy of tissue-specific structures located throughout the body. These tissue-specific rhythms are coordinated by the SCN based on light input from the outside world during daytime and by melatonin secretion during the dark cycle.

For example, during night time as it becomes darker, a message is sent to our body clock by the light-sensitive cells in the eyes, causing it to inhibit the release of hormones cortisol and adrenaline, and increase the synthesis of melatonin the sleep hormone.

Magnesium: The biological functions of magnesium are broad and varied, and include the production of nucleic acids, involvement in all adenosine triphosphate (ATP) fueled reactions, and modulation of any activity mediated by intracellular calcium concentration fluxes (e.g., insulin release, muscle contraction. Magnesium, seems to play a key role in the regulation of sleep.

• Dietary magnesium supplementation brought about statistically significant increases in sleep time (P = 0.002), sleep efficiency (P = 0.03), concentration of serum renin (P < 0.001), and melatonin (P = 0.007), and also resulted in significant decrease of Insomnia Severity Index (ISI) score (P = 0.006), sleep onset latency (P = 0.02) and serum cortisol concentration (P = 0.008)[1].
• Supplementation of magnesium appears to improve subjective measures of insomnia such as ISI score, sleep efficiency, sleep time and sleep onset latency, early morning awakening, and likewise, insomnia objective measures such as concentration of serum renin, melatonin, and serum cortisol, in elderly people[1]^,[2].
• According to our research magnesium supplementation significantly increased sleep indices and physical activity level, also resulted in significantly decrease of total calorie intake in magnesium group[2].
• An optimal level of magnesium in the body is correlated with a reduction in sympathetic system activity, low stress level, good relaxation and better sleep[iii].
• C-reactive protein (CRP) apparently readily responds by increasing with sleep deprivation. Magnesium supplementation vs placebo decreased plasma CRP in participants with baseline values >3.0 mg/L. The findings show that many individuals have a low magnesium status associated with increased chronic inflammatory stress that could be alleviated by increased magnesium intake[iv].

Glycine: a non-essential amino acid, glycine subjectively and objectively improves sleep quality in humans who have difficulty sleeping.

• A glycine-induced increase in the neuropeptides arginine vasopressin and vasoactive intestinal polypeptide in the light period[v].
• Results indicate that glycine modulated suprachiasmatic nucleus (SCN) function. Thus, glycine modulates certain neuropeptides in the SCN and this phenomenon may indirectly contribute to improving the occasional sleepiness and fatigue induced by sleep restriction[5].
• In both the peripheral and central nervous system, glycine acts as an inhibitory neurotransmitter via glycine receptors[5].
• Glycine improved subjective parameters, such as fatigue initially and objective parameters, such as psychomotor vigilance were improved on both days 1 and 3[5].
• Glycine improved subjective sleep quality and sleep efficacy (sleep time/in-bed time), and shortened polysomnography (PSG) latency both to sleep onset and to slow wave sleep without changes in the sleep architecture[vi].
• Glycine lessened daytime sleepiness and improved performance of memory recognition tasks. Thus, a bolus ingestion of glycine before bedtime seems to produce subjective and objective improvement of the sleep quality in a different way than traditional hypnotic drugs[6].

KSM-66® Organic Ashwagandha Extract is one of the few herbs with significant effects on both psychological and physiological aspects of human functioning[vii]. KSM-66® is manufactured using a water-based extraction process, without the use of any alcohol or chemical solvents, based on the principles of Green Chemistry. It supports a reduction in stress and anxiety, enhances focus, supports immune functions, and aids sleep and relaxation.

KSM-66® has the most extensive set of research studies and clinical trials; 22 studies – 11 published studies, 6 additional studies completed and in peer review and 5 ongoing studies. KSM-66 has 30 Quality Certifications including USP, NSF, UL-NPA, and WHO GMP, and is 100% Organic Certified by USDA and EU

• Serum cortisol levels: a statistically significant (p<0.05) decrease of 22.2% was observed in serum cortisol (a stress hormone) levels as a result of KSM-66® Ashwagandha supplementation, significant when compared to the placebo[viii]^,[ix]^.
• Ashwagandha is seen as a GABA-mimetic that reduces over-excitation of neurons, thereby producing calmness, reducing stress and increasing focus, mental well-being and self-control[8^,9].
• Treatment with Ashwagandha can be helpful in limiting stress-associated weight gain in humans[8^,9].

L-Theanine: research indicates that L-theanine could be beneficial for a good night’s sleep, which could be because it helps to promote relaxation. It is a unique non-proteinic amino acid that has been reported with predominant therapeutic values present almost exclusively in the tea plant (Camellia sinensis). L-theanine is thought to affect both the levels and functions of neurotransmitters in the brain. For example, L-theanine injection has been shown to raise levels of glycine, an amino acid and inhibitory neurotransmitter which helps calm one down. It raises brain levels of serotonin and GABA, two other inhibitory neurotransmitters. Finally, L-theanine may block L-glutamic acid from binding to the excitatory glutamate receptors in cortical neurons (nerve cells in the cerebral cortex).

• The relaxing effects of tea consumption have been known for decades; the active constituent of tea, called L-theanine (gamma glutamylethylamide) has modulatory effects on the brain state[x].
• It has been shown to regulate oscillatory brain activities in humans with an ability to pass through the blood–brain barrier during cognitive task execution and electroencephalographic (EEG) transcriptions and is believed to cause a relaxation effect[10].
• L-theanine has been proposed as a neuroprotective and cognitive-enhancing agent[xi].
• Peripherally and centrally administered L-theanine has been reported to act on the brain, to modulate monoamine levels in the central nervous system, and glutamate and glycine neurotransmissions[11].
• In the brain L-theanine increases dopamine and serotonin production[12^,13]
• Regardless of the mechanism, theanine increases alpha-brain wave activity, a sign of induced relaxation[12].
• Chemical structure of L-theanine is comparable to the neurotransmitters glutamate and GABA; Due to its structural similarity with glutamic acid, L-theanine is known to block the binding of L-glutamic acid to glutamate receptors in the brain, and has been considered to cause anti-stress effects by inhibiting cortical neuron excitation[xiii].
• Unlike conventional sleeping pills, L-theanine is not a sedative but induce good quality of sleep through anxiolysis[13].

Vitamin B6: Pyridoxine is believed to affect brain monoamine metabolism specifically by an alteration in the metabolism of tryptophan. It is suggested that depression may be a consequence of a decrease in the metabolism of tryptophan to 5-hydroxytryptamine (5HT) and that imbalances in the levels of steroid hormones may cause a relative deficiency of pyridoxine, the necessary co-factor in this pathway[xiv].

[1] Abbasi B, et. al., “The effect of magnesium supplementation on primary insomnia in elderly: A double‑blind placebo‑controlled clinical trial”. J Res Med Sci 2012;17:1161-9.

[2] Abbasi B, et. al., “Effect of magnesium supplementation on physical activity of overweight or obese insomniac elderly subjects: A double-blind randomized clinical trial”. Zahedan J Res Med Sci (ZJRMS) 2013; 15(3): 14-19.

[iii] Adriana Sarah Nica, et. al., “Magnesium supplementation in top athletes – effects and recommendations”, Medicina Sportiva (2015), vol. XI, no 1, 2482-2494 Journal of the Romanian Sports Medicine Society

[iv] Forrest H. Nielsen, et. al., “Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep”, Magnesium Research 2010; 23 (4): 158-68

[v] Bannai Makoto, et. al., “The Effects of Glycine on Subjective Daytime Performance in Partially Sleep-Restricted Healthy Volunteers”, Frontiers in Neurology VOLUME=3, 2012 ISSN=1664-2295 DOI=10.3389/fneur.2012.00061

[vi] Wataru Yamadera, et. al., “Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes”, Sleep and Biological Rhythms 2007; 5: 126–131

[vii] ‘Ingredient Overview: highly bioavailable, clinically effective, sustainably produced.’ www.ashwagandhaadvantage.com

[viii] ‘Ksm-66® ashwagandha / scientific studies: highly bioavailable, clinically effective, sustainably produced.’ www.ashwagandhaadvantage.com

[ix] Dnyanraj Choudhary, et. al., ‘Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial’ Journal of Evidence-Based Complementary & Alternative Medicine 2017, Vol. 22(1).

[x] Akiko higashiyama, et. al., “Effects of L-theanine on attention and reaction time response”, Journal of functional foods 3 (2011) 171–178, 2011 elsevier ltd.

[xi] Shinsuke Hidese, et. al., “Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial”, Nutrients 2019, 11, 2362

[xii] “Monograph: L-Theanine”, Alternative Medicine Review. Volume 10, Number 2, 2005

[xiii] Chatterjee, Sirshendu et.al., “L-Theanine: A Prospective Natural Medicine”, International Journal of Pharmaceutical Sciences Review and Research (2016).. 41. 95-103.

[xiv]Helen Doll et. al., “Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial”, Journal of the Royal College of General Practitioners, 1989, 39,

364-368.

Aquamin® MS Sea Minerals: our Magnesium is a Magnesium Citrate form, sourced from marine water which also contains a wide range of trace minerals. Magnesium supplementation improves sleep efficiency, sleep time and sleep onset latency, early morning awakening, and insomnia objective measures such as the concentration of serum renin, melatonin, and serum cortisol, in adults.

Glycine: a nonessential amino acid plays an essential role in the peripheral and central nervous systems. Its acts as an inhibitory neurotransmitter and improves subjective sleep quality and sleep efficacy, lessens daytime sleepiness and improves performance of memory recognition tasks.

KSM-66® Organic Ashwagandha Root Extract: our vegan KSM-66® Organic Ashwagandha is a root-only extract standardized to 5% withanolides by HPLC, which skips the milk pre-treatment and is the highest pure withanolide concentration available and acts as a GABA-mimetic that reduces over-excitation of neurons, thereby producing calmness and reduces stress.

L-Theanine: It is extracted from Green Tea Extract. The biggest benefit of L-theanine is it promotes relaxation without sedation. It can also reduce perceptions of stress and improve cognition as well as increase the alpha-brain wave activity indicates a relaxed state. Because of these properties, L-theanine is an excellent supplement to take before bed to help you “wind down”.

Vitamin B6 (as Pyridoxal 5-Phosphate): it is needed for normal brain development and function, and helps the body make the hormones serotonin and norepinephrine, which influence mood, and melatonin, which helps regulate the body clock.