Scientific Research for Hibernate-Sleep

Hibernate-Sleep

The Hibernate-Sleep formulation delivers potent adaptogenic mushrooms with Gac fruit extract for optimal sleep quality, vitality, and deep sleep duration. This formula is specifically designed for individuals struggling for a good night's sleep with poor mood and mental fatigue. It effectively decreases sleep latency time, promotes relaxation, and supports uninterrupted, restful night sleep. Moreover, optimal consumption of Hibernate-Sleep by FUNGAC Essentials Inc. improve mental stress, preserve neuronal health and help anxiety that decreases latency time for sleep and regulate disturbed sleep pattern. It is important to know that our Hibernate-Sleep formulation does not cause morning sleepiness or drowsiness. It significantly helps memory, focus, and a positive mind in the morning.

Note that Hibernate-Sleep is manufactured by a qualified expert's team in a well-certified facility using GMP guidelines. We opted for the capsule dosage form for maximum palatability and absorption. The final formulation is packed with Black Pepper Extract for maximum absorption and protection in the gastrointestinal tract.

Features of Hibernate-Sleep by FUNGAC Essentials Inc.

Natural and Pure Sleep Formulation
Free from Synthetic Chemicals
Non-GMO and Gluten Free
No Risk of Adverse Effects
Promote Sleep Duration
Decrease Sleep latency time
Improve Stress and Anxiety
Support Optimal Sleep Quality
Help Mood and Insomnia
Effective for both Men and Women
Quality Mushrooms at Cheap Price

How Does Hibernate-Sleep Works?

The highly researched supplements in the Hibernate-Sleep formula positively modulate neurotransmitters (Gamma-Aminobutyric acid (GABA), Serotonin) in the brain. As a result, it induces mild sedation, calms the nerves, decreases sleep latency, and increases total sleep duration. Additionally, the presence of passionflower, Ashwagandha, and valerian help improve anxiety, relieve mental stress, improve melatonin level and help brain functions (memory, concentration, learning capability, alertness) that increase day time work productivity. Besides, the addition of Gac Fruit Extract promotes organs vitality, protects cellular integrity, and supports optimal quality of life.

Health Benefits of Hibernate-Sleep Formulation

Fall Asleep Quickly

Hibernate-Sleep contains Valerian, Reishi, Passionflower, and Jujube extract that significantly decreases latency time for sleep, calms the overactive nerves, and helps the body fall asleep quickly. Regular consumption of Hibernate-Sleep induces sleep quicker and regulates the disturbed sleep pattern. Moreover, it prevents sleep deprivation, morning sleepiness and wakes you up energize, fresh and well-rested.

Promote Deep Sleep Duration

The presence of potent adaptogens decreases neural activity and relieves mental stress that extends quality sleep duration. Moreover, Hibernate-Sleep calms the overactive nerves, improve sleep pattern, help positive sleeping habit and support relaxation that promotes total sleep duration.

Improve Mood and Longevity

Proper consumption of Hibernate-Sleep relieves oxidative stress, anxiety and improves mood that positively impacts sleep quality and overall health and wellness. It significantly stabilizes mood, prevents sleeplessness, and increases sleep efficiency. The hibernate-Sleep composition may also aid insomnia and other sleep disorders.

Note, please read the Hibernate-Sleep label for suggested dose and precautionary measures.

References (Medical Research Studies)

Valerian Root Extract

Recorded medicinal use of valerian dates back to the first century AD. In recent years, it is popular as a sedative and hypnotic. Historically, however, its metabolic stimulating features such as diuretic, carminative, and menstrual stimulant properties had been more valued.¹⁶ It was in the middle ages that the use of valerian in treating nervous disorders and insomnia was recorded.¹⁶^,¹⁷ There are over 200 valerian species worldwide, including V. wallichii DC., V. edulis Nutt., and V. fauriei Briq., among which Valeriana officinalis L. is the most well known in Europe and North America as “valerian.” In the United States, valerian is regulated by the Food and Drug Administration (FDA) as a dietary supplement (https://ods.od.nih.gov/factsheets/Valerian-HealthProfessional/). According to the European Medicine Agency (EMA), the well-established uses of V. officinalis root include the relief of mild nervous tension as well as sleep disorders. For relief of nervous tension, recommended oral dosages are 400-600 mg dry hydroalcoholic extract or comminuted herbal substance (root) 0.3-3 g up to 3 times daily.¹⁸ Valerian is considered relatively safe and well-tolerated, however EMA monograph notes gastrointestinal symptoms (e.g. nausea, abdominal cramps) as undesirable effects. Although hydroalcoholic extracts of valerian root in the recommended dosage improve sleep latency and quality, it is uncertain what constituents contribute to the efficacy.¹⁸

The effectiveness of valerian as a sleep aid has been the major research focus, and several systematic reviews were conducted previously. A systematic review published in 2000, which analyzed 9 randomized clinical trials, found contradictory results and significant inconsistency in terms of patients, experimental design and methodology among the trials.¹⁹ Another systematic review and meta-analysis, published in 2006, analyzed 16 studies and this study also found significant methodological problems.²⁰ Taibi et al. (2007) conducted a systematic review on 37 studies, of which 29 were controlled trials and 8 were open-label trials. They concluded that, although it is a safe herb, evidence did not support the clinical efficacy of valerian as a sleep aid for insomnia.²¹ A meta-analysis of 18 randomized placebo-controlled trials, published in 2010, concluded that valerian’s effectiveness had not been demonstrated with quantitative or objective measures although valerian could improve subjective sleep quality.²² So far, these inconsistent outcomes have not been fully explained. In addition, it is not clear if valerian is effective in treating other disorders associated with, and possibly contributing to, sleep problems. The aim of the current study is to up-date the available data, to evaluate the effectiveness of valerian as a treatment of sleep problems and associated disorders, and to discuss possible reasons behind the inconsistent research outcomes, by particularly focusing on the herbal preparations used in the studies.

Sleep problems are widely prevalent and associated with various comorbidities including anxiety. Valerian (Valeriana officinalis L.) is a popular herbal medicine used as a sleep aid, however the outcomes of previous clinical studies are inconsistent. This study was conducted to update and re-evaluate the available data in order to understand the reason behind the inconsistent outcomes and to provide a broader view of the use of valerian for associated disorders. PubMed, ScienceDirect, and Cochrane Library were searched to retrieve publications relevant to the effectiveness of valerian as a treatment of sleep problems and associated disorders. A total of 60 studies (n=6,894) were included in this review, and meta-analyses were performed to evaluate the effectiveness to improve subjective sleep quality (10 studies, n=1,065) and to reduce anxiety (8 studies, n=535). Results suggested that inconsistent outcomes were possibly due to the variable quality of herbal extracts and that more reliable effects could be expected from the whole root/rhizome. In addition, therapeutic benefits could be optimized when it was combined with appropriate herbal partners. There were no severe adverse events associated with valerian intake in subjects aged between 7 and 80 years. In conclusion, valerian could be a safe and effective herb to promote sleep and prevent associated disorders.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585905/

The extract of the root of valerian (Valeriana officinalis), a flowering plant, has been widely used to treat sleeping disorders in Europe for decades.⁷ Valerian is becoming increasingly popular in the United States as a self-prescribed treatment for insomnia. In a national survey conducted in 2002, 1.1% of the adult population in the United States, or approximately 2 million adults, reported using valerian in the past week.⁸ If valerian is an effective treatment for insomnia, it may be an important treatment alternative because it is relatively inexpensive and without known side effects. We sought to clarify the efficacy of valerian for improving sleep quality by conducting a systematic review and meta-analysis of all prior randomized, controlled trials.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394901/

Valerian is one of the medicinal plants used to reduce anxiety and sleep disorders.¹³ Valerian contains 150 to 200 different substances including volatile oils, ketones, phenols, iridoid esters such as valepotriates, alkaloids, valeric acid, amino acids like aminobutyric acid, arginine, tyrosine, glutamine, and noncyclic, monocyclic, and bicyclic hydrocarbons.¹⁴ Valerian/cascade mixture significantly decreased the latency time for sleeping and increased total sleeping time. The mixture significantly increased the non-rapid eye movement sleep time, while rapid eye movement sleeping time was decreased. Electroencephalography investigation indicated decreased awakening and increased total sleep time.¹⁵ It has also been administered as a sedative-hypnotic herb for many years. Valepotriates and valerenic acid found in valerian root are responsible for the plant’s sedative and anxiolytic effects.¹⁶ Assisting sleep effect of valerian/cascade mixture was shown to be due to the upregulation of gamma-aminobutyric acid A (GABA) receptor.¹⁵ The valerenic acid contained in valerian inhibits the enzyme system responsible for the catabolism of GABA.¹⁷ Valerian and its constituents (e.g., valerenic acid) serve as GABA agonists, and the effect of the plant on GABAA receptors is similar to the effect of benzodiazepines.¹⁸ The mechanism of action of valerian has been explained by several theories. The constituents of valerian may increase GABA concentrations and decrease central nervous system activity by inhibiting the enzyme system responsible for the central catabolism of GABA.¹⁹ Valerian may also stimulate the release and reuptake of GABA and bind directly to GABAA receptors.²⁰ According to the available evidence, valerian may be the most promising agent for assisting sleep²¹ that is also considered a partial agonist of the 5-hydroxytryptamine 2A receptor that boosts melatonin release.²² Antidepressant and mood-stabilizing effects have also been proposed for valerian,²³ which could be due to the plant’s ability to interfere with noradrenergic and dopaminergic neurotransmitters, especially serotonin and GABA.¹⁷ Over the past few decades, the root extract of valerian has been widely used as a flowering plant to treat sleeping disorders in Europe.²⁴ Ziegler et al,²⁵ compared the effects of a six-week treatment with valerian extract (600 mg/day) and oxazepam (10 mg/day) in 202 patients. They found that both groups enjoyed an enhanced sleep quality, while valerian was at least equally effective as oxazepam. The effects of valerian and oxazepam were perceived to be very good by 83% and 73% of the patients, respectively.

The US Food and Drug Administration lists valerian as a food supplement with no contraindications for its use.²⁶ Valerian is a perennial herb native to North America, Asia, and Europe whose root is believed to possess sedative and hypnotic properties.²⁷

Today, valerian root extract is an accepted over-the-counter medicine for treating stress and nervous tension, disturbed sleep patterns, and anxiety in Germany, Switzerland, Belgium, Italy, and France.²⁸ Valerian can also affect sleep quality in patients with multiple sclerosis.²⁹ Studies have indicated that valerian is effective in treating anxiety and depression in menopausal women.³⁰ Valerian is a safe herbal remedy in HD.³¹ Valerian has also shown efficacy with few or no adverse effects when used correctly and following expert recommendations.²⁸ But the evidence for natural remedies is controversial and weak and is not recommended for acute or chronic sleep disorders.² Therefore, there is a tendency to use alternative and complementary therapies to assist sleep disorders.³² Further research that valerian assists sleep is required,³³ and its use as an anti-anxiety and anti-depression agent also requires further investigations.³⁴

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077445/

https://pubmed.ncbi.nlm.nih.gov/10411208/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394901/

https://pubmed.ncbi.nlm.nih.gov/10761819/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191368/

Reishi Mushroom

Three-day administration of GLE significantly increased total sleep time and non-rapid eye movement (NREM) sleep time at a dose of 80 mg/kg (i.g.) without influencing slow-wave sleep or REM sleep in freely moving rats. TNF-α levels were significantly increased concomitantly in serum, the hypothalamus, and dorsal raphe nucleus. The hypnotic effect of GLE (80 mg/kg, i.g.) was significantly inhibited by intracerebroventricular injection of TNF-α antibody (2.5 μg/rat). Co-administration of GLE (40 mg/kg, i.g.) and TNF-α (12.5 ng/rat, i.c.v.), both at ineffective doses, revealed an additive hypnotic effect.

Conclusion: These results suggest that GLE has hypnotic effects in freely moving rats. The mechanism by which the extract promoted sleep remains unclear, but this effect appears to be primarily related to the modulation of cytokines such as TNF-α. Furthermore, these data at least partially support the ethnomedical use of Ganoderma lucidum.

https://pubmed.ncbi.nlm.nih.gov/22207209/

Inflammation and insomnia are two types of symptoms very likely occur in life, seriously perplexing people's work and life. How to alleviate these symptoms is an urgent medical problem. Lucidone D (LUC) is a terpene from the ethanol extract of Ganoderma lucidum fruiting body. Triterpenoids are also the main pharmacological components of Ganoderma lucidum. In recent years, people pay more and more attention to its anti-inflammatory effect. In this study, LPS induced RAW264.7 macrophage inflammatory response model was used to evaluate the anti-inflammatory activity of LUC. The results showed that LUC could significantly inhibit the production of inflammatory mediators NO, which may play a role by down-regulating the expression level of iNOS and COX-2 proteins. Meanwhile, the production of TNF-α and IL-6 was significantly inhibited. These results indicate that LUC has obvious anti-inflammatory activity. Writhing and sedation tests in ICR male mice showed that LUC showed significant analgesic and sedative effects. In conclusion, these results suggest the anti-inflammatory, analgesic and sedative effects of LUC in vitro and in vivo.

https://pubmed.ncbi.nlm.nih.gov/31078150/

Ganoderma lucidum (G. lucidum) is a popular medicinal fungus known as Lingzhi mushroom in China. It has long been known for its beneficial effects on human health and longevity in Asian countries. G. lucidum has been shown to have several pharmacological effects (e.g., antitumor, immunomodulatory, anti-inflammatory, antidiabetic, antioxidative), which are supported by studies on various bioactive compounds isolated from the fruiting bodies and mycelia of this fungus [7]. A water-soluble extract prepared from the culture medium of G. lucidum mycelia (MAK) has a 17-year history of making appreciable contributions to consumers’ health as a safe, functional food. The extract contains various types of constituents, such as polysaccharides, including β-glucans, triterpenes, and lignin derived from the culture medium and its digestion products by the mycelia. MAK has been reported to have antitumor [8] and radioprotective effects [9].

Previously, we demonstrated that MAK has antioxidant activities and neuroprotective effects in vivo. Orally administered MAK can prevent ischemia–reperfusion-induced oxidative damage to neuronal cells, and reduce the size of cerebral infarcts in animal models [10,11]. However, until now, the antidepressant-like effects of MAK have not been assessed.

Therefore, the study aimed to assess the antidepressant-like and anxiolytic-like activities of MAK in rats. We performed the forced swimming test together with open-field test to evaluate antidepressant-like activity, and the elevated plus-maze test and contextual fear-conditioning test to evaluate anxiolytic-like activity of MAK. Furthermore, to ascertain if the antidepressant-like effect of MAK is mediated by the serotonergic system, we examined the effect of MAK on 5-hydroxy-L-tryptophan (5-HTP)- or (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI)-induced head-twitch responses.

In summary, the present study demonstrated that MAK has antidepressant-like potential, which is most likely as a result of the antagonism of 5-HT_2A receptors, and possesses anxiolytic-like effects toward memory-dependent and/or stress-induced anxiety in rats. Hereafter, further chemical and pharmacological analyses of MAK will be conducted to isolate and characterize the active ingredients responsible for these antidepressant-like effects.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879659/

Fatigue is the physical or mental exhaustion caused by overwork, exercise, and lack of sleep. It can also be a symptom resulting from medicine, illness, anxiety, or depression. Fatigue affects more than 20% of people worldwide, which is usually associated with physical and/or psychological (mental) weakness [1]. For physical weakness, the individuals engaged in vigorous activities or laborious jobs may experience reduced efficiency and capacity for work. For psychological weakness, people with depression or sleep disorders may have the sense of weariness, exhaustion, and lack of motivation [2].

The extracts of submerged fermentation of Ganoderma lucidum were also found to inhibit the accumulation of blood lactic acid, accelerate lactic acid clearance, improve glycogen reserve, and reduce glycogen consumption during exercise, resulting in less fatigue [33].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584359/

Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative tranquilizing effects. However, the component of G. lucidum that promotes sleep has not been clearly identified. Here, the effect and mechanism of the acidic part of the alcohol extract of G. lucidum mycelia (GLAA) on sleep were studied in mice. Administration of 25, 50 and 100 mg/kg GLAA for 28 days promoted sleep in pentobarbital-treated mice by shortening sleep latency and prolonging sleeping time. GLAA administration increased the levels of the sleep-promoting neurotransmitter 5-hydroxytryptamine and the Tph2, Iptr3 and Gng13 transcripts in the sleep-regulating serotonergic synapse pathway in the hypothalamus during this process. Moreover, GLAA administration reduced lipopolysaccharide and raised peptidoglycan levels in serum. GLAA-enriched gut bacteria and metabolites, including Bifidobacterium, Bifidobacterium animalis, indole-3-carboxylic acid and acetylphosphate were negatively correlated with sleep latency and positively correlated with sleeping time and the hypothalamus 5-hydroxytryptamine concentration. Both the GLAA sleep promotion effect and the altered faecal metabolites correlated with sleep behaviours disappeared after gut microbiota depletion with antibiotics. Our results showed that GLAA promotes sleep through a gut microbiota-dependent and serotonin-associated pathway in mice.

Various neurotransmitters, including GABA, 5-HT, norepinephrine and dopamine, affect different brain nuclei to regulate the switch between wakefulness and sleep³². In this study, GLAA was found to promote sleep through a 5-HT associated pathway. The monoamine neurotransmitter 5-HT, also known as serotonin, is important for sleep regulation, and animals deficient in 5-HT synthesis have been shown to stay awake longer and sleep less³². Moreover, several researchers have found that increasing the 5-HT content in the brain would prolongs sleeping time in animals, which is consistent with our results. In addition to neurotransmitters, other factors could also affect sleep, such as changes in brain structure, ion channels³³ and growth hormone²¹,²², some of which were also found in our study.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249598/

Jujube Seed

The results show that the medicinal jujube seed capsule improved the sleep quality of postmenopausal women. Thus, it could be recommended as a safe plant with fewer complications compared to chemical and hormone drugs for the treatment of sleep disorders. Also, during the period of consuming jujube seed capsule in this study, except for a few cases of gastrointestinal disorders and in similar studies with this herbal medicine, consumers have reported no specific side effects. Therefore, considering that about one-third of adults in the world suffer from sleep disorders, the high prevalence of sleep disorders in postmenopausal women, and the lower cost of treatment by jujube seed capsule compared to other treatments, it is suggested implementing this treatment as a useful method in improving sleep quality in postmenopausal women.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735973/

raditionally, one of the main functions of jujube, as described in herbal medicine, is to benefit our brain by calming down the mind and improving quality of sleep. Here, the activities of jujubes on nervous system are summarized and discussed. In Shennong Bencao Jing (300 BC-200 AD), an earlier book recoding medicinal herbs, jujube was considered as one of the superior herbal medicines that prolonged our life-span by nourishing blood, improving quality of sleep, and regulating digestive system. According to historical usage in China, one of the main functions of jujube was considered to benefit our brain by calming down the mind and improving quality of sleep. In Chinese herbal medicine, jujube was prepared as a tea that was used against insomnia [32, 33]. Indeed, jujube was found to increase pentobarbital-induced sleep time and to reduce free movement on mice [22]. In support of this, Peng et al. (2000) reported that the seed of Z. jujuba prolonged the hexobarbital-induced sleeping time in mice and decreased the locomotor activity in rats. Moreover, jujube was shown to possess anxiolytic effect by increasing the first time entry, as well as the total change and time spent in the white chamber of black and white test [34]. Besides, flavonoids and saponins from seed of Z. jujuba showed sedative and hypnotic effects, which caused a significant reduction of walking time and coordinated movement ability of mouse, significantly prolonging its sleeping time [35]. Jujuboside A, one of saponins from seed of Z. jujuba, stimulated the expression of GABA receptor subunits in rat hippocampal neurons [36] and ameliorated behavioral disorders of the dementia mouse model induced by Aβ1–42 [37]. Methanolic extract and oleamide from jujube showed activation effect on choline acetyltransferase (ChAT). Meanwhile, oleamide was found to attenuate the scopolamine-induced amnesia in mice, a useful in vivo model for Alzheimer disease [26]. Jujube was reported to improve learning and memory in ovariectomized rat model, and the effect of which might be due to an increase of estrogen in the blood, as well as the levels of nitric oxide and acetylcholine in the brain [23]. Moreover, hydroalcoholic extract of jujube was also demonstrated to possess anticonvulsant effect and amelioration of cognitive impairment induced by seizures in rats [24]. The seed extract of Z. jujuba showed a promising effect in ameliorating memory in mice with alcohol-induced memory retrieval disorders and might help to improve learning capacity to some extent [38]. In line with the aforementioned reports, jujube was reported to possess repairing effects on memory and learning impairment induced by bilateral electric lesion of the nucleus basalis of Meynert in rats [25]. In addition, jujube extract having 1% of cAMP was found to have antidepression function in animal model [39].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478819/

Semen Ziziphus jujube (SZJ), the seeds of Ziziphus jujuba Mill. var. spinosa, is a kind of traditional Chinese medicine used for its action on insomnia. In order to analyze the effective component, we investigated and compared the sedative and hypnotic effects of three kinds of compounds, flavonoids, saponins, and polysaccharides. Flavonoids, saponins, and polysaccharides were extracted from SZJ and orally administered to mice separately at 17 g kg(-1) per day for certain days before animal tests. Spontaneous motility and coordinated movement tests were used to observe the effects of the three kinds of compounds on the mouse behavior, and sodium barbital-induced sleeping time of mouse were tested to analyze the effects of the three kinds of compounds on the sleep of mouse. Results show that flavonoids and saponins caused a significant reduction of walking time and coordinated movement ability of mouse, significantly prolonged its sleeping time at 40 mg kg(-1), ip, subthreshold dose and increased the sleeping number of animals at 50 mg kg(-1), ip, superthreshold dose induced by coeliac injection of sodium barbital. Polysaccharides did not show any significance in all animal tests. Comparative analysis showed that saponins had a more effective sedative and hypnotic function than that of flavonoids, polysaccharides did not show a sedative and hypnotic effect.

https://pubmed.ncbi.nlm.nih.gov/17479419/

Passion Flower

Passiflora incarnata induced a significant increment in the total sleep time (p<0.05). This increment was due to an increase in the time spent by animals in slow wave sleep (SWS). Concomitantly, a significant decrement in wakefulness (W) was observed (p<0.05). In contrast, time spent in rapid eye movement (REM) sleep showed a decreasing tendency, since both its frequency and mean duration were reduced.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699852/

On the other hand, Passiflora incarnata L. (PI) has been widely used in South America for several centuries, showing effectiveness for sleep, sedation, anxiety, and so on in the civilian population. However, reports on the treatment efficacy of this herbal medicinal plant for insomnia patients through standardization as a sleeping agent have been very rare. Therefore, we obtained leaves and fruits of PI (8:2 by weight) as powder to prepare an extract. It was then applied to C6 rat glioma cells to quantitate mRNA expression levels of GABA receptors. Its sleep‐inducing effect was investigated using experimental animals. PI extract (6 μg/ml) significantly decreased GABA receptors at 6 hr after treatment. Immobility time and palpebral closing time were significantly increased after single (500 mg/kg) or repeated (250 mg/kg) oral administration. In addition, blood melatonin levels were significantly increased in PI extract‐treated animals after both single and repeated administrations. These results were confirmed through several repeated experiments. Taken together, these results confirmed that PI extract had significant sleep‐inducing effects in cells and animals, suggesting that PI extract might have potential for treating human insomnia.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977488/

Passiflora incarnata is a traditional herbal sedative, anxiolytic and a popular sleep aid used for the treatment of sleep disturbance. Several controlled experiments have demonstrated enhanced sleep in laboratory animals, but clinical trials in humans are lacking. The aim of the present study was to investigate the efficacy of Passiflora incarnata herbal tea on human sleep, as measured using sleep diaries validated by polysomnography (PSG). This study featured a double-blind, placebo-controlled, repeated-measures design with a counterbalanced order of treatments (passionflower vs placebo tea), separated by a 1 week 'washout' period. Forty-one participants (18-35 years) were exposed to each treatment for a week, whereby they consumed a cup of the tea and filled out a sleep diary for 7 days, and completed Spielberger's state-trait anxiety inventory on the seventh morning. Ten participants also underwent overnight PSG on the last night of each treatment period. Of six sleep-diary measures analysed, sleep quality showed a significantly better rating for passionflower compared with placebo (t(40) = 2.70, p < 0.01). These initial findings suggest that the consumption of a low dose of Passiflora incarnata, in the form of tea, yields short-term subjective sleep benefits for healthy adults with mild fluctuations in sleep quality.

https://pubmed.ncbi.nlm.nih.gov/21294203/

https://pubmed.ncbi.nlm.nih.gov/29410738/

These results indicate that PI treatment was effective in increasing GABAergic neuron activity and blood melatonin levels, evidenced by a significant decrease of EE observed at the time when mice are generally active in the dark cycle. In other words, no increase in appetite or increase in body weight was observed, and any body compositions were not changed; only sleeping was changed. Since there have been reports of behavioral abnormalities and metabolic changes that may be caused by the repeated use of diverse prescribing sleeping pills, we tried to find out whether the repeated administration of PI extract may cause such problems in the animal models. Taken together, we did not find any side effects of abnormal metabolic phenotypes or behaviors, such as hyperphagia or unexpected metabolic changes by repeated administration of PI extract to mice for 5 days (Additional file 2). We confirmed the use of PI extract showed only sleep-inducing effects, at least in animal models, without causing any adverse behavioral or metabolic disorders through this study.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081546/

Insomnia, or sleep disturbance, is a sleep disorder symptom characterized by difficulty in falling sleep or maintaining sleep, resulting in a “short” or “shallow” sleep. As a symptom, it causes problems with the quantity or quality of sleep, and chronic insomnia is associated with headaches, depression, anxiety disorders, and other health problems.6,7 Traditionally, Passiflora incarnata L. is a plant that has been used to treat insomnia. Several studies have shown clinically relevant benefits of Passiflora incarnata L. for insomnia treatment. In one double-blind, placebo-controlled study, 41 participants (18–35 years) drank a cup of tea made with Passiflora incarnata L. and wrote in a sleep diary for seven days and 10 of these participant underwent overnight polysomnography on the last night. Analyzing the sleep diary, sleep quality was significantly better in the tea-drinking group compared to the placebo group (t = 2.70, P < 0.01). This study shows that Passiflora incarnata L. has a potential effect on quality of sleep.8

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770524/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699852/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977488/

https://pubmed.ncbi.nlm.nih.gov/21294203/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5139955/

https://www.karger.com/Article/Fulltext/464342

https://pubmed.ncbi.nlm.nih.gov/30951822/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521387/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203277/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081546/

https://www.ncbi.nlm.nih.gov/books/NBK548020/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770524/

Ashwagandha (Withania somnifera)

Ashwagandha root extract is a natural compound with sleep-inducing potential, well tolerated and improves sleep quality and sleep onset latency in patients with insomnia at a dose of 300 mg extract twice daily. It could be of potential use to improve sleep parameters in patients with insomnia and anxiety, but need further large-scale studies.

Sleep actigraphy (Respironics Philips) was used for assessment of sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE) and wake after sleep onset (WASO). Other assessments were total time in bed (sleep log), mental alertness on rising, sleep quality, Pittsburgh Sleep Quality Index (PSQI), and Hamilton Anxiety Rating Scale (HAM-A) scales.

Results

Two patients, one from each group, did not complete study and the per-protocol dataset (n = 58) included 29 and 19 patients from test and placebo, respectively. The baseline parameters were similar in the two groups at baseline. The sleep onset latency was improved in both test and placebo at five and 10 weeks. However, the SOL was significantly shorter (p, 0.019) after 10 weeks with test [29.00 (7.14)] compared to placebo [33.94 (7.65)]. Also, significant improvement in SE scores was observed with Ashwagandha which was 75.63 (2.70) for test at the baseline and increased to 83.48 (2.83) after 10 weeks, whereas for placebo the SE scores changed from 75.14 (3.73) at baseline to 79.68 (3.59) after 10 weeks. Similarly, significant improvement in sleep quality was observed with test compared to placebo (p, 0.002). Significant improvement was observed in all other sleep parameters, i.e., SOL, SE, PSQI and anxiety (HAM-A scores) with Ashwagandha root extract treatment for 10 weeks.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827862/

In both healthy and insomnia subjects, there was a significant improvement in the sleep parameters in the Ashwagandha root extract supplemented group. The improvement was found more significant in insomnia subjects than healthy subjects. Repeat measure Analysis of variance (ANOVA) confirmed the significant improvement in SOL (p 0.013), HAM-A outcomes (p < 0.05), mental alertness (p 0.01), and sleep quality (p < 0.05) of the insomnia patients. A two-way ANOVA was used to confirm the outcomes that denoted sleep onset latency (p < 0.0001) and sleep efficiency (p < 0.0001) as the most improved parameters, followed by TST (p < 0.002) and WASO(p < 0.040). All these parameters (SOL, TST, WASO, TIB, SE, PSQI, HAM-A, Mental Alertness, and Sleep quality) were also statistically assessed for the significant improvement within the group both for the treatment, and the placebo groups in the healthy and the insomnia datasets. Obtained results suggest statistically significant (p < 0.0001) changes between the baseline values and the end of the study results except for the HAM-A and the mental alertness scoresn the healthy subject group. The present study confirms that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Ashwagandha root extract was well tolerated by all the participants irrespective of their health condition and age. Additional clinical trials are required to generalize the outcome.

https://pubmed.ncbi.nlm.nih.gov/32818573/

A total of 144 subjects completed the study, with no dropouts due to adverse events. A 72% increase in self-reported sleep quality was found for the treatment group, compared with 29% in the placebo group (p < 0.001). Based on activity monitoring data, the treatment group showed significant improvement in sleep efficiency (SE) (p < 0.01), total sleep time (p < 0.001) and sleep latency (p < 0.01) and wake after sleep onset (WASO) (p < 0.05) versus placebo after six weeks. In the ashwagandha group quality of life (QOL) scores showed significant improvement in physical (p < 0.001), psychological (p < 0.001), and environment domains (p < 0.01).

Conclusions: Supplementation with the standardized ashwagandha extract for six weeks improved the overall quality of sleep by significantly improving the NRS condition in healthy subjects. No treatment related adverse events were reported in the study.

https://pubmed.ncbi.nlm.nih.gov/32540634/

Sleep deprivation disrupts significantly sleep pattern and cause poor quality of sleep. The aim the present study was to explore role of Withania somniferra root extract in sleep-disturbed rats. Male wistar rats (n=5-6/group) were sleep deprived for 24 h using grid suspended over water method. Withania somniferra extract (100 mg/kg) was administered intraperitoneally (i.p.) 30 min before actual recording (EEG and EMG) recording and electrophysiological recordings are further classified as- sleep latency, slow wave sleep, paradoxical sleep, total sleep, wakefulness. One day (24 h) sleep deprivation delayed latency sleep, reduced duration of slow wave sleep, rapid eye movement sleep, total sleep time and increased total waking as compared to animals placed on saw dust (P<0.05). Pretreatment with Withania somniferra extract (100 mg/kg) and diazepam (0.5 mg/kg) significantly improved electrophysiological parameters, which was further reversed by picrotoxin (2 mg/kg) and potentiated by muscimol (0.05 mg/kg). Flumazenil (2 mg/kg) did not produce any significant effect on the sleep parameters of Withania somnifera root extract. Present study suggests the involvement of GABAergic mechanism in the sleep promoting effect of Withania somniferra in sleep-disturbed state.

Pretreatment with Withania somnifera shortened sleep latency, decreased waking, increased NREM and total sleep time in sleep-disturbed rats. These indicated that Withania somnifera may have their role in sleep promotion in sleep-disturbed states and can be employed as drugs for the management of sleep and related problems. Diazepam that augments the action of GABA at the GABA_A receptor, shortened sleep latency; decreased waking, increased NREM and total sleep time significantly as compared to control (sleep-deprived animals). The above observations again reconfirm the hypnotic action of diazepam in sleep-disturbed state. In the present experiment, diazepam, when administered in combination with Withania root extract did not improve sleep promotion of Withania root extract in sleep-disturbed animals.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040882/

Ashwagandha induced a calming anxiolytic effect that was comparable to the drug Lorazepam in all three standard Anxiety tests: the elevated plus-maze, social interaction and the feeding latency in an unfamiliar environment. Further, both Ashwagandha and Lorazepam, reduced rat brain levels of tribulin, an endocoid marker of clinical anxiety, when the levels were increased following administration of the anxiogenic agent, pentylenetetrazole.

Ashwagandha also exhibited an antidepressant effect, comparable with that induced by imipramine, in two standard tests, the forced swim-induced ‘behavioral despair’ and ‘learned helplessness’ tests. The investigations support the use of Ashwagandha as a mood stabilizer in clinical conditions of anxiety and depression. (Abdel-Magied et al., 2001)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252722/

In this eight-week, prospective, randomized, double-blind, placebo-controlled study, the stress-relieving effect of Ashwagandha root extract was investigated in stressed healthy adults. Sixty male and female participants with a baseline perceived stress scale (PSS) score >20 were randomized to receive capsules of Ashwagandha extract 125 mg, Ashwagandha extract 300 mg or identical placebo twice daily for eight weeks in a 1:1:1 ratio. Stress was assessed using PSS at baseline, four weeks and eight weeks. Anxiety was assessed using the Hamilton-Anxiety (HAM-A) scale and serum cortisol was measured at baseline and at eight weeks. Sleep quality was assessed using a seven-point sleep scale. A repeat measures ANOVA (general linear model) was used for assessment of treatment effect at different time periods. Post-hoc Dunnett’s test was used for comparison of two treatments with placebo.

Results

Two participants (one each in 250 mg/day Ashwagandha and placebo) were lost to follow-up and 58 participants completed the study. A significant reduction in PSS scores was observed with Ashwagandha 250 mg/day (P < 0.05) and 600 mg/day (P < 0.001). Serum cortisol levels reduced with both Ashwagandha 250 mg/day (P < 0.05) and Ashwagandha 600 mg/day (P < 0.0001). Compared to the placebo group participants, the participants receiving Ashwagandha had significant improvement in sleep quality.

Conclusion

Ashwagandha root aqueous extract was beneficial in reducing stress and anxiety.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979308/

This 12-week, prospective, randomized, double-blind, placebo-controlled study was conducted on individuals of either gender aged between 65-80 years. Participants were randomized to receive Ashwagandha root extract at a dose of 600 mg/day (n = 25) orally, or identical placebo capsules with the same dose (n = 25) for 12 weeks. Efficacy was assessed using the WHOQOL-BREF questionnaire, sleep quality, mental alertness on rising, and Physician’s Global Assessment of Efficacy to Therapy (PGAET). The safety and tolerability were assessed using the clinical adverse events reporting and Patient's Global Assessment of Tolerability to Therapy (PGATT).

Results

Statistically significant (P<0.0001) improvement was observed in the Ashwagandha treatment group compared to the placebo. The mean (SD) total score of WHOQOL-BREF improved from 140.53 (8.25) at the baseline to 161.84(9.32) at the end of the study. The individual domain scores were also improved. At baseline, the sleep quality and the mental alertness on rising were comparatively low in both the groups. However, upon intervention, a significant increase in the quality of sleep (P<0.0001) and mental alertness (P<0.034) was observed in the Ashwagandha treatment group when compared to the placebo group. Overall improvement was observed for the general wellbeing, sleep quality, and mental alertness in the study population. The experimental group population displayed good tolerability to the test product and it was reported as safe and beneficial by the study participants.

Conclusion

The study outcomes suggest that Ashwagandha root extract was efficient in improving the QoL, sleep quality, and mental alertness as self-assessed by the elderly participants. The recommended dose used in this study could be effective for the elderly population.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096075/

Insomnia is the most common sleep complaint which occurs due to difficulty in falling asleep or maintaining it. Most of currently available drugs for insomnia develop dependency and/or adverse effects. Hence natural therapies could be an alternative choice of treatment for insomnia. The root or whole plant extract of Ashwagandha (Withania somnifera) has been used to induce sleep in Indian system of traditional home medicine, Ayurveda. However, its active somnogenic components remain unidentified. We investigated the effect of various components of Ashwagandha leaf on sleep regulation by oral administration in mice. We found that the alcoholic extract that contained high amount of active withanolides was ineffective to induce sleep in mice. However, the water extract which contain triethylene glycol as a major component induced significant amount of non-rapid eye movement sleep with slight change in rapid eye movement sleep. Commercially available triethylene glycol also increased non-rapid eye movement sleep in mice in a dose-dependent (10–30 mg/mouse) manner. These results clearly demonstrated that triethylene glycol is an active sleep-inducing component of Ashwagandha leaves and could potentially be useful for insomnia therapy.

Insomnia and poor quality of sleep results in chronic sleep loss that is associated with various other sleep and metabolic disorders. Unlike conventional therapy available to treat insomnia, those develop dependency and side effects, we were interested to identify a natural compound with sleep-inducing potential. In this study, we demonstrated that TEG, which is also an active component of Ashwagandha leaves, is a potent sleep-inducing small molecule. Ashwagandha leaf or root crude powder itself is able to enhance the quality of sleep.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313221/