THE SCIENCE OF HIBERN8
HOW DOES HIBERN8 WORK?
THE 4 SILO FUNCTIONS
SILO 1 - Magnesium Threonate and L Theanine synergistically combine to provide increased REM sleep.
Magnesium Threonate has been selected in the Hibern8 ingredients because of its unique property of absorption into the brain. It's a form of magnesium, chemically known as L-Threonic acid Magnesium salt, which effectively crosses the blood-brain barrier.
L-Theanine is an amino acid predominantly found in tea leaves, specifically in green tea. L-Theanine promotes relaxation without causing drowsiness or sedation. It works by increasing the levels of calming brain chemicals like serotonin and GABA, which can modulate sleep. Simultaneously, it reduces levels of chemicals associated with stress and anxiety. Also L-Theanine enhances alpha brain waves, associated with a state of wakeful relaxation.
L-theanine and Magnesium can both help increase the amount of GABA in the body. GABA is a neurotransmitter that has calming and relaxing effects on the body, and can help induce sleep. Taking both of these natural supplements can increase the amount of time you spend in restful REM sleep. L-theanine may also help prevent sleep disturbances and reduce feelings of stress, which can make it easier to fall asleep faster and stay asleep throughout the night. Additionally, magnesium helps to relax the muscles and promote relaxation and deeper sleep.
SILO 2 - PEA and Caralluma Fimbriata extract joint Gencor ingredient profile. Acute and long term benefits of anti-inflammatory and anxiolytic properties via CB1 receptors and PPAR-α. To help with duration on sleep.
Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide that belongs to the family of endocannabinoids, which are lipid molecules produced in the body. It is synthesized from palmitic acid, a saturated fatty acid, and ethanolamine, a simple organic compound. Palmitoylethanolamide is present in various tissues and cells throughout the body, playing a crucial role in maintaining homeostasis and regulating several physiological functions.
Palmitoylethanolamide (PEA) promotes better sleep via potential interaction with the endocannabinoid system. Although PEA does not directly bind to cannabinoid receptors like THC (tetrahydrocannabinol) or CBD (cannabidiol), it exerts its effects by influencing the endocannabinoid system in a more indirect manner.
SILO 3 - Tart cherry and Griffonia Simplicifolia (5-HTP) in indirect - Serotonin and Melatonin production. Helps with onset of sleep.
The combination of tart cherry and 5-HTP may improve sleep. Tart cherry is rich in melatonin, a hormone produced naturally in the human body which helps regulate our sleep patterns. In addition, 5-HTP can assist the body in releasing more serotonin, which helps the body create more melatonin. It has been suggested that this dual action from tart cherry and 5-HTP can work together synergistically to improve overall sleep quality.
Tart cherries contain high concentrations of melatonin, a hormone that helps to regulate our body's sleep-wake cycle. By increasing melatonin levels, tart cherry can help to promote and maintain healthy sleep. Additionally, tart cherries contain certain compounds that have been found to reduce stress and anxiety, which can help to promote feelings of relaxation and allow one to drift off into a peaceful sleep with ease.
SILO 4 - Chamomile extract, Ashwaghanda and Vitamin B6
Chamomile extract has been shown to act as a allosteric modulator of the GABA-A receptor complex. Animal studies have reported that Chamomile extract has a potentiating effect on GABA-mediated effects, which suggests that it could have a potential therapeutic application in the treatment of anxiety and other neurological disorders.
Chamomile extract has been shown to interact with Vitamin B6, resulting in an increase in the bioavailability of the nutrient. Clinical studies have demonstrated that a combination of Chamomile extract and Vitamin B6 can help reduce levels of homocysteine in the blood. Where high levels of homocysteine in the brain can interfere with melatonin and sleep.
Additionally, it has been suggested that Chamomile extract and Vitamin B6 may also play a role in the synthesis of neurotransmitters in the brain and help support cognitive function.
Ashwagandha, a herb popular in traditional Ayurvedic medicine, is known for its adaptogenic properties, meaning it helps the body adapt to stressors and maintain balance. Its potential to support sleep arises from several mechanisms including -
Stress Reduction: by lowering cortisol levels, it can help calm the nervous system and promote relaxation, which is essential for falling asleep.
Anxiety Relief through anxiolytic (anti-anxiety) properties, which can help alleviate symptoms of anxiety and promote a sense of calmness conducive to better sleep.
Regulation of GABA (gamma-aminobutyric acid), a neurotransmitter known for its calming effects on the brain. Ashwagandha has been found to enhance the activity of GABA receptors, leading to a calming effect on the central nervous system, which can aid in inducing sleep.
SUPPORTING JOURNALS
Silo 1 - L-Theanine and Magnesium Threonate
Michael R Lyon, Mahendra P Kapoor, Lekh R Juneja. 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. Pubmed: Altern Med Rev. 2011 Dec;16(4):348-54.
Summary:
Double blind, 97 participants boys with ADHD given 400mg theanine daily (two doses of 200mg) for 6 weeks, the ADHD-related disturbances in sleep appeared to be attenuated. A significant improvement in sleep efficiency (more time asleep relative to awake) and movement during sleep was noted, with trends towards improved scores on WASO. Sleep latency and duration appeared unaffected.
Shinsuke Hidese, Shintaro Ogawa, Miho Ota, Ikki Ishida, Zenta Yasukawa, Makoto Ozeki, Hiroshi Kunugi. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Pubmed: Nutrients. 2019 Oct 3;11(10):2362. doi: 10.3390/nu11102362.
Summary:
A double-blind randomized, placebo-controlled, crossover trial to examine the effects of 4 weeks of L-theanine administration (200 mg/day) vs. placebo on stress-related symptoms and cognitive functions in 30 healthy male and female adults with no major psychiatric illness. While statistically significant within-group effects are noted in the theanine treatment arm and not in the placebo arm for several variables, the between-group comparisons (theanine vs. placebo) are not statistically significant and, therefore further studies would need to be performed.
Jerome Sarris, Gerard J Byrne, Lachlan Cribb, Georgina Oliver, Jenifer Murphy, Patricia Macdonald, Sonia Nazareth, Diana Karamacoska, Samantha Galea, Anika Short, Carolyn Ee, Yoann Birling, Ranjit Menon, Chee H Ng. L-theanine in the adjunctive treatment of generalized anxiety disorder: A double-blind, randomised, placebo-controlled trial. J Psychiatr Res. 2019 Mar:110:31-37. doi: 10.1016/j.jpsychires.2018.12.014. Epub 2018 Dec 8.
Summary:
In a randomized, double-blind, placebo-controlled trial 46 participants with generalized anxiety disorder were allocated to take 450 mg of theanine (in two divided doses of the course of the day, or placebo for 8 weeks. The primary outcomes were anxiety and insomnia. There was a small advantage of theanine for insomnia, However further study would be required.
Katja Held, I A Antonijevic, H Künzel, M Uhr, T C Wetter, I C Golly, A Steiger, H Murck. Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pubmed: Pharmacopsychiatry. 2002 Jul;35(4):135-43. doi: 10.1055/s-2002-33195.
Summary:
Magnesium for 20 days via effervescent tablets (10-30mmol) was associated with improved sleep in elderly persons.Forrest H Nielsen, LuAnn K Johnson, Huawei Zeng. Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Pubmed: Magnes Res. 2010 Dec;23(4):158-68. doi: 10.1684/mrh.2010.0220. Epub 2011 Jan 4.
Forrest H Nielsen, LuAnn K Johnson, Huawei Zeng. Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Pubmed: Magnes Res. 2010 Dec;23(4):158-68. doi: 10.1684/mrh.2010.0220. Epub 2011 Jan 4.
Summary:
The findings, suggest an association between magnesium status and sleep quality that needs further study to definitively determine whether a low magnesium status is a cause or an effect of poor sleep quality.
Silo 2 - PEA and Caralluma fimbriata
Amanda Rao, Phillippa Ebelt, Alistair Mallard and David Briskey. Palmitoylethanolamide for sleep disturbance. A double-blind, randomised, placebo-controlled interventional study. BMC Sleep Science Practice 2021; 5:12
Summary: These findings support PEA as a potential sleeping aid capable of reducing sleep onset time and improving cognition on waking.
Evangelista M, Cilli, De Vitis R, Militerno A, Fanfani F. Ultra-micronized Palmitoylethanolamide Effects on Sleep-wake Rhythm and Neuropathic Pain Phenotypes in Patients with Carpal Tunnel Syndrome: An Open-label, Randomized Controlled Study. CNS Neurol Disord Drug Targets. 2018;17(4):291-298. doi: 10.2174/1871527317666180420143830. PMID: 29676237.
Summary: There was a highly significant improvement in overall sleep quality with an increase of continuous sleep time and a reduction of sleep latency and disturbances.
Ramaswamy, Rajendran & Ambikar, Digambar & Khandare, Rakesh & Sannapuri, Vrushali & Vyawahare, Niraj & Clayton, Paul. (2014). Nootropic Activity of Caralluma fimbriata Extract in Mice. Food and Nutrition Sciences. 05. 147-152. 10.4236/fns.2014.52019.
Summary: CFE has significant nootropic and anxiolytic activity in mice. Its nootropic/anxiolytic/anorexogenic profile makes it a candidate treatment for Prader-Willi Syndrome.
Lama A, Pirozzi C, Severi I, Morgese MG, Senzacqua M, Annunziata C, Comella F, Del Piano F, Schiavone S, Petrosino S, Mollica MP, Diano S, Trabace L, Calignano A, Giordano A, Mattace Raso G, Meli R. Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice. Brain Behav Immun. 2022 May;102:110-123. doi: 10.1016/j.bbi.2022.02.008. Epub 2022 Feb 14. PMID: 35176443; PMCID: PMC10662208.
Summary: PEA treatment promoted an improvement in anxiety-like behavior of obese mice and the systemic inflammation, reducing serum pro-inflammatory mediators (i.e., TNF-α, IL-1β, MCP-1, LPS). The results strengthen the therapeutic potential of PEA in obesity-related neurotransmitter imbalance involved in behavioral dysfunctions.
G. Kell, A. Raob, M. Katsikitisa. A randomised placebo controlled clinical trial on the efficacy of Caralluma T fimbriata supplement for reducing anxiety and stress in healthy adults over eight weeks. Journal of Affective Disorders 246, 2019; 619–626
Summary: The findings indicate that CFE is superior to placebo in reducing subclinical anxiety and stress over 8 weeks.
Qi Chen, Chunyan Ji, Ruihe Zheng, Longhe Yang, Jie Ren, Yitian Li, Yun Han, Pan Zhou, Zuguo Liu, Yan Qiu. N-Palmitoylethanolamine Maintains Local Lipid Homeostasis to Relieve Sleep Deprivation-Induced Dry Eye Syndrome. Pubmed Front Pharmacol 2020 Jan 28:10:1622
Summary:
The nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) was found to mediate the PEA-associated improvements. We describe here for the first time that PEA is involved in sleep deprivation-induced lacrimal gland pathogenesis and dry eye development.
Silo 3 - Tart Cherry and Griffonia Simplicifolia
Tart CherryLosso JN, Finley JW, Karki N, Liu AG, Prudente A, Tipton R, Yu Y, Greenway FL. Pilot Study of the Tart Cherry Juice for the Treatment of Insomnia and Investigation of Mechanisms. Am J Ther. 2018 Mar/Apr;25(2):e194-e201. doi: 10.1097/MJT.0000000000000584. PMID: 28901958; PMCID: PMC5617749.
Summary:
Tart Cherry juice increased sleep time and sleep efficiency. Cherry juice procyanidin B-2 inhibited IDO, increased tryptophan availability, reduced inflammation and may be partially responsible for improvement in insomnia.
Howatson G, Bell PG, Tallent J, Middleton B, McHugh MP, Ellis J. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. Eur J Nutr. 2012 Dec;51(8):909-16. doi: 10.1007/s00394-011-0263-7. Epub 2011 Oct 30. PMID: 22038497.
Summary:
The data suggest that consumption of a tart cherry juice concentrate provides an increase in exogenous melatonin that is beneficial in improving sleep duration and quality in healthy men and women and might be of benefit in managing disturbed sleep.
Shell W, Bullias D, Charuvastra E, May LA, Silver DS. A randomized, placebo-controlled trial of an amino acid preparation on timing and quality of sleep. Am J Ther. 2010 Mar-Apr;17(2):133-9. doi: 10.1097/MJT.0b013e31819e9eab. PMID: 19417589.
Summary :
2010 study showed that a combination of 5-HTP and (GABA) significantly reduced the time it took to fall asleep, increased sleep duration, and improved sleep quality.
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 Apr 1;150:42-9. doi: 10.1016/j.lfs.2016.02.086. Epub 2016 Feb 26. PMID: 26921634.
Summary:
5-HTP improves sleep quality and that the effect is greater when combined with GABA.
Hong KB, Park Y, Suh HJ. Sleep-promoting effects of the GABA/5-HTP mixture in vertebrate models. Behav Brain Res. 2016 Sep 1;310:36-41. doi: 10.1016/j.bbr.2016.04.049. Epub 2016 May 2. PMID: 27150227.
Summary:
Evidence suggests that the GABA/5-HTP mixture modulates both GABAergic and serotonergic signaling. Moreover, the sleep architecture can be controlled by the regulation of GABAA receptor and GABA content with 5-HTP.
Silo 4 - Ashwaghanda, Vitamin B6 and Chamomile extract.
K Chandrasekhar, Jyoti Kapoor, Sridhar Anishetty. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Pubmed - Indian psychologist Med 2012 Jul;34(3):255-62. doi: 10.4103/0253-7176.106022.
Summary: 600 mg of an ashwagandha extract ("full spectrum") for 60 days in persons with chronic mental stress was able to improve all tested parameters and reduced serum cortisol by 27.9%.
Jaysin Salve, Sucheta Pate, Khokan Debnath, Deepak Langade. Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Punmed - Cureus 2019 Dec 25;11(12):e6466. doi: 10.7759/cureus.6466.
Summary:The improvements in sleep quality were greater for both ashwagandha groups than for placebo, and the greatest for the high dose group. Notable differences between groups for adverse events weren't found.
Deepak Langade, Subodh Kanchi, Jaising Salve, Khokan Debnath, Dhruv Ambegaokar. Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study. Pubmed - Cureus 2019 Sep 28;11(9):e5797. doi: 10.7759/cureus.5797.
Summary:Sleep quality on The Pittsburgh Sleep Quality Index (PSQI) was improved more in the ashwagandha group, and the difference was statistically significant, and as was the score on the Hamilton Anxiety Rating Scale (HAM-A).
Cooley K, Szczurko O, Perri D, Mills EJ, Bernhardt B, Zhou Q, Seely D. Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974. PLoS One. 2009 Aug 31;4(8):e6628. doi: 10.1371/journal.pone.0006628. PMID: 19718255; PMCID: PMC2729375.
Summary: 300 mg ashwagandha (1.5% withanolides) twice daily over the course of 8 weeks in persons with anxiety disorders also given counselling (placebo also given counselling) noted that supplementation was associated with a 56.5% reduction in anxiety symptoms as assessed by BAI while placebo only say a 30.5% reduction.