Ashwagandha (Withania somnifera): Effect of extract on sleep

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Winter cherry, Indian ginseng, and Ajagandha, Queen of Ayurveda, called by so many names, Withania somnifera Dunal (Ashwagandha; Family-Solanaceae), is a plant used in ayurvedic medicine in the traditional system and indicated for the management of several neurological disorders.

Ashwagandha (ASH) is a Rasayana of Ayurveda – a real potent regenerative tonic possessing several pharmacological properties, such as neuro-protective, anti-stress, anti-arthritic, antitumour, analgesic and anti-inflammatory [1]. 

Fresh  root of the Ashwagandha herb ‘smells like horse’ so-called Ashwagandha, because there is the belief that anyone who consumes the herb is given the power and strength of a horse) [1, 2, 3].

It is also referred to as a ‘royal herb’ possessing multiple therapeutic effects in the different human body systems: immune system, neurological and endocrinal system, the aerobic energy-production system, as well as the reproductive system [3, 4]. The presented study depicts the miraculous role of Ashwagandha in Ayurveda possessing versatile medicinal properties empowering human physical and mental health.

Versatile roles of Ashwagandha.

Ashwagandha as a whole plant including each part serves therapeutic uses (Table 1). Several therapeutic properties of ashwagandha are associated with presence of chemical consituents in the herb (Table 2). In the era of evidence-based medicine research and innovation is a practical phenomenon [5]. Ashwagandha has been also used successfully in ayurvedic research.

Rasayana

Ashwagandha as a herb promotes the health of body and brain by increasing stress tolerance and reinforcing the immune system. Ashwagandha is available as churna, a fine powder that can be mixed with water or ghee honey which has various medicinal benefits. It improves the memory and increases the function of the central nervous system (CNS) [5, 6].

This miraculous benefit of the herb has been proved by a study in which the Morris water maze test was conducted to assess the effect of W. somnifera, where rats pre-treated with the herb showed significant alterations towards normal in comparison to control groups (disease group) [7–10].

The Morris water maze test and maze test were also used in a study to assess the effect of W. Somnifera on 3-NP (3-nitropropionic acid) induced Huntington’s disease (HD) [11]. In both tests the Morris water maze and maze test, W. somnifera (100 and 200 mg/kg) treatment for two

weeks significantly restored 3-NP induced memory loss. Neurodegenerative disorders cause memory loss and W. Somnifera has been found to improve learning ability with potential protection against memory loss. In  one  study, the effect of the herb on cognitive dysfunction induced by reserpine was investigated by using plus maze learning task Withania somnifera root extract (50 and 100 mg/kg/day for one month) significantly improved the long-term memory and learning ability in reserpine-treated animals, compared to those treated only with reserpine [12, 13].

Withania somnifera leaf extract has been found to ease cognitive dysfunction by showing improved hippocampal plasticity in a high fat diet (HFD) induced obesity model. Ashwagandha has been found to significantly improve working memory by preventing the memory related cognitive impairments and locomotor coordination in high fat diet rats. During locomotor coordination studies it was observed that HFD rats showed deficiency in interest and strength, whereas ASH treated low fat diet extract (LFDE) and high fat diet extract (HFDE) rats performed similarly to low fat diet (LFD) rats, indicating their normal neuromuscular coordination. Findings from the behavioural studies revealed that HFD regimen caused locomotor and neuro-muscular dysfunction, and ASH proved the potential to improve motor performance and body balance in rats on an HFD regimen [14].

During the novel drug development process, assessment of drug effects on psychomotor performance is truly essential. In clinical pharmacological studies psychometric tests are performed to quantitatively document the CNS effects of drugs. Effects of drugs on the central nervous system (CNS) can be assessed in the form of effects on attention, vigilance, cognition, behaviour, and neuro-physiological activity of the brain. Withania somnifera improves the brain’s cognitive capabilities by increasing the capability of muscarinic receptors [15]. Pingali et al. demonstrated favourable effects of  Withania  somnifera  aqueous  extract on  cognitive and

psychomotor performance in healthy human participants in which several psychometric tests were performed using a computerized psychometric test system [16]. Withania somnifera has been found to modulate the neuro-endocrino- immune system and is known as brain tonic rich in anti- oxidants, especially in the field of Ayurveda. Clinical trials have proved the anti-depressant activity of the herb without causing any sedative effect. It eases the mental stress bundle with resultant optimization of mental and psychomotor
performance [17].
Sitoindosides VII-X and withaferin-A derived from leaf and fruit extracts of Withania somnifera has been found to increase cortical muscarinic acetylcholine capacity by its cognition-enhancing effect, as seen in animal models and humans [15]. It was found in a randomized, double-blind study that Withania somnifera showed improved psychomotor performance in healthy participants with significant improvement in integrated sensorimotor function, auditory reaction tim, as well as mental arithmetic as compared to Panax ginseng and placebo in 30 healthy volunteers [18].

Adaptogen
Ashwagandha acts as a plant which helps the body to adapt to stress in order to correct the imbalance among immune and neuroendocrine system. It normalizes the body functions affected by the influence of stress by targetingthe hypothalamic-pituitary-adrenal gland axis. Ashwagandha decrease cortisol levels in a person under chronic stress, restoring the healthy adrenal function and thus normalizing the sympathetic nervous system [3].
Somnifera (sleep-inducing). In a study of effect of alcoholic and water extracts of Ashwagandha leaves on the quality and quantity of sleep, significant electroencephalogram (EEG) and electromyogram (EMG) changes were seen in an animal model (mice). Ayurveda, the traditional medicine system of India, also supported that an increase in sleep was observed after administration of extracts from leaf and root in rats, and after oral consumption of the powder obtained from root, leaves or whole plant in humans. Tri-ethylene Glycol (TEG), an active component of Ashwagandha leaves, is a potent sleep-inducing small molecule. Sleep regulation has two components viz sleep generation, i.e. frequency of NREM episodes and sleep maintenance duration NREM episodes. TEG is able to generate sleep more frequently, thus increasing the total amount of NREM sleep. TEG also promotes physiological sleep, i.e. naturally occurring sleep in healthy individuals. TEG was found to increase the frequency of NREM sleep episodes, which suggests that it has a potential to generate sleep via targeting the sleep generation mechanism [3].

Ojas
Ojas is the end condition of properly digested healthy food, and the most refined level of the physical body in contrast to ‘Ojakshaya’ (decreased Ojas) which refers to a condition similar to AIDS/HIV. Ojas is responsible for a healthy immune system, physical strength, clarity of mind and sense of well-being. It allows consciousness to flow within the body. Ashwagandha enhances Ojas. Ashwagandha in the form of churna when used on a regular basis helps to improve conditions like senile debility, rheumatism, general debility, nervous exhaustion, brain-fog, low memory, loss of muscular energy and spermatorrhoea. It increases vigour and body energy and helps in rebuilding the body system worn-out as a result of chronic diseases like syphilis and rheumatism [19].
Improving the quality of life. Ashwagandha plays an important role in improving the quality of life and performance at work. These diseases affecting the quality of life are mentioned in table.3 along with International Classification of Diseases (ICD) code [20] and various pharmacologic actions and interactions of Ashwagandha are listed in Table 4.
Effects of Ashwagandha observed in other conditions. Male sexual dysfunction: Ashwagandha root extract is used to treat sexual weakness, erectile dysfunction, and sexual performance anxiety in men.
Immunostimulation – immunity stimulating effect through macrophages. Raised antibody titer against Bordetella pertusis strains (combats diphtheria).
Reproductive action and rejuvenating effect – increases libido and sexual function. Supports the female reproductive system, increases ovarian weight and folliculogenesis; a rejuvenative herb in the Indian herbal system Ashwagandha as a cardiovascular protector protects the cardiovascular system against ischemic and reperfusion injury; useful in focal ischemia, supports anti-atherogenic activity in polyherbal formula [21, 32].

Pharmacological interactions of Ashwagandha.

Pregnancy – safety in pregnancy has not been yet fully established for Ashwagandha. Ashwagandha has been reported to be a cause of abortions; therefore pregnant women should not use this herb. It should also not be used with other sedatives or anti-anxiety drugs. Even higher doses are observed to be related with stomach upset, diarrhea and vomiting. However, Ashwagandha does not have any significant side-effects. [21] and has been found to possess pharmacologic interactions listed in Table 5.


Table 2. Chemical constituents of Ashwagandha

Chemical constituentTherapeutic roleMechanismReference
Triethylene glycol (TEG)sleep induction.TEG promotes physiological sleep i.e. naturally occurring sleep in healthy individuals.[3]
Withanolidesanti-cancer activity, neuroprotection and anti- stress activity, recovery from amnesia, anti-mutagenic.slows down the growth of lung, colon, breast and cancer cells;acts as growth inhibitor in human tumour cell lines counteracting mutagenic effect;improves cellular immune response to mitogens;reverses paclitaxel- induced neutropenia;respected as a natural source of potent radiosensitizer in chemotherapy;useful in melanoma- induced metastasis. 
Sitoindoside, withanolidesprotects cells from oxidative damage and disease.eliminates free radicals from immune syste; has a good effect in iron overload and lead toxicity; prevents neuroleptic- induced extra-pyramidal side-effects;increases natural antioxidants in the brain;stimulates the immune system through nitric oxide production in macrophage. 
Sitoindoside VII and sitoindoside VIII, sitoindoside IX and Xanti-stress activity, stress- induced gastric ulcer.used as ginseng in chronic stress models;protects from stress- induced neuronal degeneration;helps in achieving a better state to fight against stress.prevents stress-related ulcer. 
Sitoindoside IX and Ximmunomodulatory and central nervous system effects with impact on memory, stress and learning.used as Medhya Rasayanas Medhya (mind and mental/intellectual capacity) this cognition- promoting action of the herb as Medhya Rasayanas is observed best in cases of compromised memory post head injury, or after prolonged illness, and in geriatrics or in case of children 
Glycowithanolides withaferin- A and sitoindosides VII–X isolated from the rootssignificantly reversed ibotenic acid induced cognitive defects.L-dopa found in Ashwagandha enhances memory via cholinergic channels; stabilizes mood and improves learning ability.[2, 8]
Diseases affecting quality of life and work performanceICD CODETherapeutic effects of ashwagandhaReference
InsomniaG47.00TEG in Ashwagandha is able to generate sleep more frequently.[3, 21–25]
OsteoarthritisM19protects against inflammation and cartilage damage associated with osteoarthritis.
AnxietyF41anti-anxiety action similar to that of lorazepam, together with effect to ease depression.
Type 2 diabetesE11helps normalize high blood sugar and improves insulin sensitivity 

Table 3. Diseases affecting quality of life with ICD code and therapeutic effects of Ashwagandha

Diseases affecting quality of life and work performanceICD CODETherapeutic effects of ashwagandhaReference
InsomniaG47.00TEG in Ashwagandha is able to generate sleep more frequently.[3, 21–25]
OsteoarthritisM19protects against inflammation and cartilage damage associated with osteoarthritis.
AnxietyF41anti-anxiety action similar to that of lorazepam, together with effect to ease depression.
Type 2 diabetesE11helps normalize high blood sugar and improves insulin sensitivity 

Table 4. Pharmacological Actions of Ashwagandha

Pharmacologic actionFindings from preclinical studiesReference
Anxiolytic effectAshwagandha and lorazepam reduced brain levels of tribulin (an endocoid marker of clinical anxiety) in rats following administration of the anxiogenic agent pentylenetetrazole which raises the levels.[2]
Anti-depressant effectAnti-depressant effect is comparable to the effect produced by imipramine, in learned helplessness and forced swim-induced ‘behavioural despair’ tests.
Gaba-mimetic effect on neurodegeneration and neuroregenerative potentialThe herb, its constituents and metabolites of its constituents promote the growth of nerves after consumption for a week. Gaba-mimetic activity having anxiolytic effect. Inhibiting cholinesterase and thereby retaining acetylcholine for longer time. Induction of axon and dendrite outgrowth, thereby resulting in neuritis regeneration and synaptic reconstruction
Anti-Parkinson’s effectPre-treatment with Ashwaganda extract was found to protection of the neuronal injury in parkinson’s disease in a dose- dependent manner 
Analgesic activityAshwagandha (1000 mg/kg/oral) produced significant analgesic activity in a rat experiencing heat analgesia induced by hot plate method.
Acute toxicity studiesLD50 of Withania somnifera was found to be 1750 mg (p.o.) in albino mice. 
Anti-tumour effectEffect on Chinese Hamster Ovary (CHO) cells carcinoma. Ashwagandha inhibits cell growth and prevents cell attachment. Inhibitory effect of Withania roots was observed in up to 49% on the colony forming efficiency of CHO cells, dependent on the cell density and duration of Ashwagandha exposure.

Table 5. Pharmacologic interactions of Ashwagandha

Ashwagandha interaction typeEffects observedClinical evidenceExperimental evidenceMechanismReference
Anti-diabeticblood-glucose lowering effects which may be additive with conventional anti-diabeticsPresentNo interactions found.Not known[26–31]
Ashwagandha + methods of measuring serum digoxin levelsdigoxin levels might be spuriously elevated when assayed using a fluorescence polarisation immunoassay in patients takingNo interactions foundPresentKnown. Some withanolides (major constituents of ashwagandha) are structurally similar to digoxin, and might therefore interfere with the digoxin immunoassay
Ashwagandha + Laboratory testsno interference with in vitro assays for carbamazepine, gentamicin, paracetamol, phenytoin phenobarbital, procainamide, salicylate, theophylline, tobramycin or valproic acidNo interactions foundNo interactions foundNo 
Ashwagandha + FoodNo interactions foundNo interactions foundno 
Ashwagandha + herbal medicinesNo interactions foundNo interactions foundno 
Ashwagandha + thyroid and anti-thyroid drugsincreases thyroid hormone levels and found to interfere with the control of hypo- and hyperthyroidismPresentPresentUnknown 

Sleep is a state of reversible unconsciousness in which the brain is less responsive to external stimuli [1]. Throughout the period of sleep, the body will cycle periodically between non-rapid eye movement (NREM) sleep and rapid-eye-movement (REM) sleep. NREM sleep is further divided into four stages, which is a continuum of relative depth [2].

Sleep episode in adults starts with a brief period of NREM stage 1, the lightest sleep stage. It progresses through NREM stage 2, stage 3 and stage 4, the deepest sleep stage. NREM sleep is then followed by REM sleep, which is known for the most vivid dreams and bodily movements. The cycle is repeated three to six times, and as sleep episode progresses, the duration of stages of NREM sleep shorten while the duration of REM sleep lengthens [3].

Healthy sleep is essential for neural development, learning, memory, cardiovascular and metabolic regulation. Sufficient sleep is needed to provide recovery after preceding waking activities and ensure optimal functioning during subsequent wakefulness [4]. As recommended by the National Sleep Foundation, in a healthy individual, the recommended sleep duration for younger adults is seven to nine hours, and for older adults is seven to eight hours [5].

In general, sleep duration decreases with increasing age. In a meta-analysis that involved 5273 healthy adults, total sleep time decreased by approximately 10 minutes for each decade of age [6]. However, there is no ideal duration of sleep required per night. A generally accepted assumption is that amount of sleep is enough if the individual wakes up feeling well-rested and perform well during the day [7].

Other than adequate duration, healthy sleep comprises good quality. A systematic review in 2016, involving 277 studies, has identified all possible sleep indicators and came out with the first sleep quality recommendation, which the National Sleep Foundation endorsed. Sleep continuity variables including 1) sleep latency of 15 minutes and less, 2) one or fewer awakening of more than five minutes per night, 3) wake time after sleep onset of 20 minutes and less, and 4) sleep efficiency of 85% and more are indicators of good sleep quality regardless of age [8]. However, no consensus reached regarding sleep architecture or nap-related variables as an indicator of good sleep quality. In general, studies have shown that the percentage of NREM sleep increases and the percentage of REM sleep decreases with increasing age. Older adults tend to have less consolidated sleep with more frequent awakenings [9].

Studies have reported a decline in sleep duration and sleep quality over the years in many modern societies. This is shown in a 27-year follow up study of United States adults where the percentage of adults sleeping six hours and less has increased by 31% from 1985 to 2012. In China, 11% of adults slept six hours and less per day [10–12]. While in an Italian study involving 3120 adults, 14% reported sleep dissatisfaction, and 30% has insufficient sleep [13]. Other than a decline in sleep quantity and quality, the prevalence of insomnia disorder also shows an increasing trend. It ranges from 3.9% to 22.1%, with an average of approximately 10% for multinational studies that used the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria [14]. The incidence is even higher in older adults, where 50% reported having sleep problems [15].

Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity or quality. It is defined in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) as a subjective complaint of difficulty initiating sleep, difficulty maintaining sleep, or early morning awakenings that occur at a minimum of three nights per week for three months, and associated with one or more daytime symptom such as fatigue, cognitive impairment or mood disturbance. In comparison to the DSM-IV, the distinction into primary and secondary insomnia, whether the insomnia is comorbid with or caused by other disorders, was replaced by the term “insomnia disorder” in DSM-5. This shift reflects that insomnia is now recognized as an independent disorder [16].

Despite the progress made in understanding the aetiology and pathophysiology of the disorder, there is no universally accepted model. In 2015, Levenson and colleagues presented a model of the pathophysiology of insomnia after looking into findings at various levels of analysis [17]. They proposed that insomnia is most likely to develop in those who have a genetic vulnerability and have abnormalities in neurobiological processes. These vulnerabilities may lead to neurophysiologic hyperarousal and psychologic and behavioural processes, which, individually or together, increase an individual’s risk of developing insomnia and associated downstream health consequences. Precipitating stressors and other person-specific factors such as age and sex moderate these relationships. However, each of these processes varies among different individuals.

There is increasing evidence of the consequences of short sleep duration. Study shows that a short period of sleep restriction for three days can significantly increase sleepiness, fatigue, stress, and decreased functioning [18]. Several systematic reviews have reported the association between short sleep duration and the increased risk of hypertension [19, 20], type 2 diabetes mellitus [21], obesity [22], metabolic syndrome [23], coronary heart disease [24], and stroke [25]. A systematic review in 2017 has shown that short sleep duration, defined as less than six hours of sleep per 24 hours, is associated with a significant mortality increase [26]. All the studies demonstrated that an adequate amount and good-quality sleep are essential for overall quality of life (QoL).

Insomnia is generally treated using pharmacological and non-pharmacological approaches. Commonly used pharmacological agents include benzodiazepine receptor agonists, sedating antidepressants, sedating antihistamines, melatonin receptor agonists, and dual orexin receptor antagonists [27]. However, most of these available drugs might develop dependency and/or adverse effects. Hence, non-pharmacological treatment is generally considered the first-line treatment for a sleep disorder. Non-pharmacological treatments include cognitive-behavioural therapy for insomnia, sleep hygiene, psychotherapy, and relaxation techniques [28].

Although cognitive-behavioural therapy for insomnia is the preferred choice of non-pharmacological therapy for insomnia, it is underutilized because of a scarcity of its providers. Hence, complementary and alternative therapies gain increasing popularity in the treatment options of insomnia. These include massage, music therapy, aromatherapy, acupuncture and/or acupressure and herbal medicine. Sleep problems were rated one of the five most common conditions in people seeking complementary and alternative medicine treatments, including herbal products [29].

One of the herbal therapies currently under investigation for insomnia is Withania somnifera, commonly known as Ashwagandha. It has been used for centuries for various purposes in Ayurveda, the traditional system of medicine in India. It is an evergreen, straight, branching shrub that originates in Western India and Mediterranean regions [30]. The roots of plants are considered the most important part of the whole plant, as they are rich in bioactive molecule, especially withanolides, which is responsible for their medicinal property [31]. Other parts of the plant, such as its stem and leaves, also contain several bioactive molecules [32].

There is an increase in demand in Ashwagandha in the form of dietary supplements. Ashwagandha extracts from its root, leaves or combination of two is marketed in many forms, but pills and capsules are the commonest [30]. Researches have shown that it possesses anti-inflammatory, anti-cancer, anti-stress, anti-oxidant, immunomodulatory, hemopoietic and rejuvenating properties [33, 34]. Extracts obtained from the roots and leaves have been used for multiple purposes, such as rheumatic pain, joints inflammation, cognitive disorders, anxiety and stress disorders, male infertility, and improvement in physical performance [35–39].

Ashwagandha extract is generally well tolerated. A study has shown the haematological and biochemical organ function safety of Ashwagandha even in higher doses ranging from 6–10 gm of crude pulverized roots administered in aqueous extract form [40]. The exact mechanism is unknown. In an earlier study, Ashwagandha was thought to induce sleep through GABAergic activity, as seen in sleep-deprived rats [41]. Withanolides, the major biologically active constituents of Ashwagandha roots and leaves, are believed to be responsible for the majority of biological functions of Ashwagandha. However, Kaushik and colleagues noted ethanol extract that contains a high ratio of withanolides has failed to induce sleep in mice, indicating that withanolides might not be involved in sleep promotion [42]. A more recent study found that the triethylene glycol (TEG) in water extract is responsible for sleep in mice. TEG induces sleep by increasing the number of NREM episodes and decreasing the duration of the wake episode. However, studies on the effect of Ashwagandha related to insomnia in human are limited.

Poor sleep poses a great public health concern. It causes morbidities and huge economic loss to society through traffic accident, less productivity at work, and clinical cost for the treatment [43]. Although it is expected, sleep problem remained underdiagnosed and undertreated. Due to possible side effects from currently available pharmacological treatment for insomnia [27], herbals utilization for sleep problems has been growing. Although Ashwagandha extract has been reviewed extensively for its use in many medical purposes, its effect on sleep has not been reviewed. Hence, evaluation of the effects and safety of Ashwagandha on sleep can provide a basis for use decisions. The main objective of this review is to determine the effect of the Ashwagandha extract on sleep.

Discussion
This review was designed to examine the evidence for the effect and safety of Ashwagandha extract on sleep in adults. The meta-analysis of five trials revealed evidence for a clinically beneficial effect of Ashwagandha extract compared to placebo in improving sleep. A small but significant improvement in overall sleep was observed with a reduction of 0.59 units. The evidence of effect was noted for Sleep Quality Scale using seven-point scale, sleep onset latency, total sleep time, wake time after sleep onset, and sleep efficiency. The effects were more prominent in adults diagnosed with insomnia, treatment dose ≥600 mg/day, and treatment duration ≥8 weeks. However, there were insufficient trials to examine the effect on participant’s age. We found that Ashwagandha extract significantly improved mental alertness on rising and anxiety but no significant effect on the QoL. In term of safety, reporting of adverse events was limited to minor side effects.

We performed a comprehensive and extensive literature review to assess the effect of Ashwagandha extract on sleep in adults. In this review, we included five trials with 400 participants, with only one trial that studied elderly adults. With the limited data, the findings of this review might not be applicable to the elderly population. Besides, trials published in the non-English language were not included. We might unintentionally miss unpublished reports or trials published in languages other than English. However, a recent meta-epidemiological study showed that excluding non-English studies from systematic reviews does not change conclusions [57].

There are some limitations to this review that are worth noting. There are many tools available to assess sleep quantity and quality, yet there is no consensus on what method should be used [58]. Three trials included in this review used actigraphy to assess sleep quality objectively. Although lab-based polysomnography is considered the gold standard for the assessment of sleep, it is not commonly used due to higher cost, more invasive, and it disrupts participants’ usual sleep routines [59].

In contrast, actigraph is cheaper, less invasive, more convenient, and has been widely used as a validated alternative to assess sleep [59–62]. While there is much evidence on the application of actigraphy, it is essential to recognize that it does not directly measure sleep. Still, it measures movement, which is then used to estimate sleep/wake cycles. Hence, the result by actigraphy may be affected by movement disorders and other conditions [63].

As for the subjective measurement of sleep quality, two tools were used in the trials. Pittsburgh Sleep Quality Index is the most widely used subjective measurement of sleep quality, and had been one of the most rigorously validated tools used in sleep diagnostics [64–66]. In this review, only two of the trials used this tool. On the other hand, the seven-point Sleep Quality Scale which was used by four of the other reviewed trials was not commonly used, and not found in previous review. Moreover, the findings from the four trials were inconsistent and the sample size was small. Hence, the findings may be an overestimation and thus required more study in the future.

The overall level of evidence in this review ranged from low to high. In general, a low or unclear risk of bias was judged for most trials in most domains. The risk of selection bias was unclear in one trial [45], as the detail of allocation concealment was not mentioned. The risk of attribution bias was present in one trial, given a relatively high drop-out rate due to non-compliance to intervention [55]. Loss to follow-up was less than 20% in the other four trials. There was no evidence of selective reporting bias. Still, we cannot exclude this because only one of the trials had published protocol and only two were prospectively registered on a trial registration database. We encountered serious inconsistency for some of our primary outcomes on sleep quality and quantity. Substantial heterogeneity was noted for overall sleep, sleep by sleep quality scale, sleep by Pittsburgh Sleep Quality Index, sleep efficiency, sleep by participant’s background with and without insomnia, sleep by treatment dosage ≥600 mg/day, and treatment duration ≥8 weeks. Serious imprecision was found on most of our primary outcomes due to the small sample size of the trials included in this review.

We attempted to reduce publication bias by checking the reference lists of all related studies for further references and searching multiple databases without restriction on publication date. However, we cannot be certain that we have located all the trials in this area. We contacted Ashwagandha extract manufacturers for further trials, but we have had no response to date. Due to limited trials, we could not construct a funnel plot for detecting publication bias.

To date, there is no other systematic review and meta-analysis that has explicitly examined the effect of Ashwagandha extract on sleep outcome in human trials. These meta-analysis results are partly in line with previous systematic reviews that examine Ashwagandha extract in other health aspects. Lopresti et al. recently published a systematic review that examined the effect of Ashwagandha extract on health and physical/cognitive performance in human trials [67]. Out of the 41 human trials that were reviewed, seven trials were on stress and anxiety, one trial on insomnia, and one trial on general well-being. Three of the trials were included in our review [53–55], and Lopresti et al. concluded that Ashwagandha extract has a positive effect on anxiety, insomnia, and general well-being. In this review, we found that Ashwagandha extract had a significant effect on sleep outcome and anxiety but no significant effect on the QoL. Besides, our result on improvement in anxiety was similar to a previous systematic review that examined the effect of Ashwagandha extract on anxiety [36].

In term of safety, reporting of adverse events was limited to minor side effects. Therefore, Ashwagandha extract seems to be relatively safe for use in improving sleep. This is in line with the finding from previous exploratory study [40].

Authors’ conclusion
Ashwagandha extract appears to have a beneficial effect in improving sleep, both subjectively and objectively, in adults. In this meta-analysis, KSM-66 and Shoden® were the two Ashwagandha extract used. KSM-66 was used in four out of the five included trials. As it seems to be a relatively safe intervention, it can be considered an option in improving sleep until new evidence is available. Ashwagandha extract with a dosage ≥600 mg/day and treatment duration ≥8 weeks seem more effective. However, data in this review on the serious adverse effects of Ashwagandha extract are limited, and more safety data would be needed to assess whether it would be safe for long-term use.

If further research were to be done to examine the effect of Ashwagandha extract on sleep, the standardized Ashwagandha extract preparation, dosage, and duration of treatment should be determined. There are various brands of Ashwagandha extract in different form and dosage in the market, and hence standardization of extract preparation and dosage would be beneficial. The trials that we included in this review were conducted, on average, for ei

ght weeks. Thus, there is a paucity of clinical evidence regarding the long-term safety and efficacy of Ashwagandha extract on sleep. Besides, only two trials combined subjective and objective sleep assessments in this review. Further research should use valid subjective and objective sleep measurement tools to produce a more validated outcome [59]. The lack of data on the effects of Ashwagandha extract usage in the elderly warranted that more research is needed on this population since insomnia is more common in this age group [68].


reference link :https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462692/

  • http://www.jpccr.eu/Ashwagandha-Withania-somnifera-a-herb-with-versatile-medicinal-properties-empowering,141582,0,2.html
  • doi: 10.26444/jpccr/141582

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