|No.||References||Outcomes / Benefits||Effective/Recommended Dosage|
|1||Byun, J., Shin, Y., Chung, S., & Shin, W. (2018). Safety and Efficacy of Gamma-Aminobutyric Acid from Fermented Rice Germ in Patients with Insomnia Symptoms: A Randomized, Double-Blind Trial. Journal Of Clinical Neurology, 14(3), 291. https://doi.org/10.3988/jcn.2018.14.3.291||– Sleep latency was significantly reduced for fermented rice germ extract containing GABA (RFE-GABA) intake compared to placebo intake.|
– RFE-GABA intake also improved subjective sleep quality and reduced the symptom severity in subjects with insomnia.
– Patients who suffer from insomnia can benefit from RFE-GABA intake without suffering severe adverse events.
|Gamma-aminobutyric acid (GABA; 300 mg daily) extracted from unpolished rice germ|
|2||Yamatsu, A., Yamashita, Y., Pandharipande, T., Maru, I., & Kim, M. (2016). Effect of oral γ-aminobutyric acid (GABA) administration on sleep and its absorption in humans. Food Science And Biotechnology, 25(2), 547-551. https://doi.org/10.1007/s10068-016-0076-9||– GABA significantly shortened sleep latency and increased the total non-rapid eye movement (non-REM) sleep time.||112mg GABA powder (100 mg GABA + 4.7 mg Glutamic acid, 2.3 mg other amino acids, 3.4 mg minerals and 1.6 mg water|
|3||Yamatsu, A., & et al. (2015). The Beneficial Effects of Coffee on Stress and Fatigue can be Enhanced by the Addition of GABA ―A Randomized, Double‒blind, Placebo Controlled, Crossover‒designed Study―. Japanese pharmacology & therapeutics, 43(4), 515 – 519.||– GABA exhibited its stress-reducing and fatigue-relieving effect even in coffee.|
– Coffee itself also showed stress-reducing effect, and the effects of coffee was enhanced by the addition of GABA.
|20 mg GABA + 280 ml coffee|
|4||Tarleton, E., Littenberg, B., MacLean, C., Kennedy, A., & Daley, C. (2017). Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PLOS ONE, 12(6), e0180067. https://doi.org/10.1371/journal.pone.0180067||– Magnesium plays a role in many of the pathways, enzymes, hormones, and neurotransmitters involved in mood regulation.|
– In low magnesium states, high levels of calcium and glutamate may deregulate synaptic function, resulting in depression.
– Magnesium is effective for mild-to-moderate depression in adults, works quickly and is well tolerated without the need for close monitoring for toxicity.
|248 mg of elemental magnesium daily|
|5||Abbasi, B., Kimiagar, M., Sadeghniiat, K., Shirazi, M. M., Hedayati, M., & Rashidkhani, B. (2012). The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 17(12), 1161–1169.||– 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 insomnia objective measures such as concentration of serum renin, melatonin, and serum cortisol, in elderly people.||500 mg elemental magnesium daily|
|6||Pouteau, E., Kabir-Ahmadi, M., Noah, L., Mazur, A., Dye, L., & Hellhammer, J. et al. (2018). Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. PLOS ONE, 13(12), e0208454. https://doi.org/10.1371/journal.pone.0208454||– Both Mg–vitamin B6 and Mg alone reduced stress from baseline to Week 8 by approximately 40% in the overall adult population sample.|
– In people with severe or extremely severe stress with low serum magnesium concentration, the Mg–vitamin B6 combination provided a 24% greater reduction in stress than Mg alone at Week 8.
– These clinical data support the use of Mg supplementation to reduce stress in stressed adults with low serum magnesium concentrations.
– The results provide clinical support for a superior benefit of Mg combined with vitamin B6 in a 10:1 ratio in adults with severe stress.
|Magnesium–vitamin B6; daily dose 300 mg and 30 mg magnesium alone; daily dose 300 mg|
|7||Djokic, G., Vojvodic, P., Korcok, D., Agic, A., Rankovic, A., & Djordjevic, V. et al. (2019). The Effects of Magnesium – Melatonin – Vit B Complex Supplementation in Treatment of Insomnia. Open Access Macedonian Journal Of Medical Sciences, 7(18), 3101-3105.||– Magnesium is a muscle relaxant and inducer of the deeper sleep.|
– 3 months of the Magnesium-melatonin-vitamin B complex supplementation has a beneficial effect in the treatment of insomnia regardless of cause.
|Magnesium-melatonin-vitamin B complex (one dose contains 175 mg liposomal magnesium oxide, 10 mg Vitamin B6, 16 μg vitamin B12, melatonin 1 mg, Extrafolate-S 600 μg)|
|8||Evans, M., McDonald, A., Xiong, L., Crowley, D., & Guthrie, N. (2021). A Randomized, Triple-Blind, Placebo-Controlled, Crossover Study to Investigate the Efficacy of a Single Dose of AlphaWave® l-Theanine on Stress in a Healthy Adult Population. Neurology And Therapy, 10(2), 1061-1078. https://doi.org/10.1007/s40120-021-00284-x||– AlphaWave® L-Theanine significantly increased frontal region alpha power compared to placebo in response to an acute stress challenge.|
– These changes are indicative of relaxation in the brain and suggest a calming response. AlphaWave® L-Theanine was found to be safe and well tolerated by participants.
|AlphaWave® L-Theanine (200 mg)|
|9||Thiagarajah, K., Chee, H., & Sit, N. (2022). Effect of Alpha-S1-Casein Tryptic Hydrolysate and L-Theanine on Poor Sleep Quality: A Double Blind, Randomized Placebo-Controlled Crossover Trial. Nutrients, 14(3), 652. https://doi.org/10.3390/nu14030652||– The supplement prolonged the total sleeping time by 45 min in the supplement receiving group compared to the placebo group||RLX2™ (150 mg Alpha-S1-Casein Tryptic Hydrolysate and 50 mg L-theanine)|
|10||Hidese, S., Ogawa, S., Ota, M., Ishida, I., Yasukawa, Z., Ozeki, M., & Kunugi, H. (2019). Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients, 11(10), 2362. https://doi.org/10.3390/nu11102362||– For stress-related symptoms, Self-rating Depression Scale, State-Trait Anxiety Inventory-trait, and Pittsburgh Sleep Quality Index (PSQI) scores decreased after L-theanine administration.|
– The PSQI subscale scores for sleep latency, sleep disturbance, and use of sleep medication reduced after L-theanine administration, compared to the placebo administration.
– For cognitive functions, verbal fluency and executive function scores improved after L-theanine administration.
|L-theanine (200 mg/day)|
|11||Ferracioli-Oda, E., Qawasmi, A., & Bloch, M. (2013). Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders. Plos ONE, 8(5), e63773. https://doi.org/10.1371/journal.pone.0063773||– Decreased sleep latency by 7.1 minutes, increased total sleep time by 8.3 minutes, improved overall sleep quality, and had a favorable adverse effect profile.|
– Trials with longer duration and using higher doses of melatonin demonstrated greater effects on decreasing sleep latency and increasing total sleep time.
|0.1 mg to 5 mg melatonin|
|12||Wurtman, R. (2014). Low Doses of Melatonin Promote Sleep Onset and Maintenance in Older People—An Update. US Neurology, 10(02), 117. https://doi.org/10.17925/usn.2014.10.02.117||– A very small dose (0.3 mg) of melatonin is usually sufficient to restore nighttime plasma melatonin levels to those characteristic of young people, and to accelerate the resumption of sleep after premature awakenings.|
– The much larger doses that are marketed can produce side effects that are not observed when the melatonin in the plasma derives solely from its secretion by the pineal.
– Very high doses may also desensitize melatonin’s receptors in the brain, subsequently diminishing melatonin’s efficacy in promoting sleep.
|0.3 mg melatonin|
|13||Lee, R. (2018). Anxiety. Integrative Medicine, 46-52.e1. https://doi.org/10.1016/b978-0-323-35868-2.00006-2||– 5-HTP has been used as an oral supplement alternative to boost serotonin.|
– It has been shown in studies to improve depression, but only preliminary evidence is available suggesting that 5-HTP also may improve anxiety.
|For anxiety or depression, the dose is 150 to 800 mg daily.|
Remark:- Kindly check with local regulatory teams on ingredients regulatory legal compliance.