Valerian

Valerian is the common name for the plant Valeriana officinalis, which is a species of plant in the Valeriana genus (of the Valerianaceae family). Its traditional uses are as a nightly sedative and as an anxiolytic tea, ^[1] and is a particularly popular option for insomnia, with historical reports of this herb being used in Greece up to 2,000 years ago.^[2]

Valeriana officinalis is a medicinal plant, traditionally used to aid sleep and prevent insomnia.

There is also a plant known as 'Indian Valerian' (Valeriana wallichii) while having some similarities to both Valerian officinalis and patchouli, should be considered a different supplement than Valerian officinalis.^[3]

For supplementation purposes, valerian refers only to the officinalis species of the plant Valeriana officinalis, as other species may have very different biological and chemical compositions.

Valerian (root unless otherwise specified) tends to contain:

• Valerenic acid (seen as the main bioactive) usually standardized to 0.8-1% of the final product^[4][5] alongside hydroxyvalerenic acid and acetoxyvalerenic acid^[4]
• (Irioid valepotriates) at 0.5-2.0%^[6] of which include valtrate, isovaltrate, didrovaltrate, acevaltrate
• (Lignans) 8'-hydroxypinoresinol and pinoresinol-4-O-β-d-glucoside (0.20% of a methanolic root extract; collectively 36% of total lignans^[7] and both comparable in quantity to one another^[4]),^[8] massoniresinol-4'-O-β-d-glucoside (0.01-0.069%^[4]), 4'-O-β-d-glucosyl-9-O-(6"-deoxysaccharosyl)olivil (0.053%), and berchemol-4'-O-β-d-glucoside at 0.04-0.049%^[4] (7,9'-monoepoxylignans)^[7] and pinoresinol-4,4'-di-β-O-d-glucoside (0.109-0.41%^[4]), 8-hydroxypinoresinol-4'-O-β-d-glucoside (0.045%), and 8'-hydroxypinoresinol-4'-O-β-d-glucoside at 0.024% (7,9‘:7‘,9-diepoxylignans) ^[7]
• (Sequesterpenes) Volvalerenone A^[9]
• (Flavonoids) of which include 6-methylapigenin and hesperidin (0.2%^[4])^[10] as well as linarin (Acacetin rhamnoglucoside^[11]) at 0.002%^[4]
• Chlorogenic acid at 1.157% (powder dry weight)^[4]

The essential oil of valerian (0.2%–2.8% dry weight) includes:

• (Monoterpenes) Borneol and bornyl acetate
• (Sequesterpenes) Valerenic acid, valeric acid, isovaleric acid, acetoxyvalerenic acid, valerenal glycol, valeranone glycol, and kessyl glycol

The major bioactive of Valeriana officinalis is valerenic acid, which is found in the essential oil of the root.

Valerenic acid, the main bioactive in valerian, will degrade a small amount when stored at room temperature (20% over 500 days).^[12] Acetoxyvalerenic acid also degrades at room temperature. Its degredation product, along with valernic acid's, is hydroxyvalerenic acid, which increases 5-fold while total sequesterpen levels drop by 30%.^[12]

Valerenic acid is mostly stable during storage, although minor degradation may occur over a prolonged period of time.

Valerian root has a strong scent in 70% ethanolic extract, which is its most common extract. ^[13] This has been a problem for blinded studies involving valerian.^[14]

Extracts of Valeriana officinalis, used as a dietary supplement, have a powerful aroma.

The standard extract of valerian tends to be an aqueous:ethanolic extract (30:70) of the roots, which usually has a concentration in the range of 4-7:1 (four to seven-fold concentrated) and is standardized for an 0.8% valerenic acid content.^[15] The recommended dosage is in the 400-900mg range assuming the aformentioned standardization,^[1] with some studies using up to 1,600mg over the course of the day and lower doses (400-600mg) being used as a one-time dosage taken an hour before sleep, since some trials comparing 450mg to 900mg for sleep failed to note any significant benefit with the higher dose.^[16][17]

The standard supplement form of Valeriana officinalis is a 70% ethanolic extract, standardized at 0.8% valerenic acid. One dose is 450mg, usually taken an hour before sleep. If taken during the day, a slightly increased dose, taken two to three times a day with meals, should be used instead.

There is a fixed combination of valerian and hops (humulus lupulus) known as Ze91019, which is used as a sleep aid in Europe;^[18] supplementation of Ze91019 provides 250mg of a methanolic root extract of valerian and 60mg of the hops extract (also methanolic).^[18][19]

This combination appears to be a methanolic extract with a drug:extract ratio of 4–6:1 for valerian (4-6 times concentrated) and 5–7:1 for the hops, and has around 0.388% total valerenic acids (0.173% valerenic acid and 0.215% acetovalerenic acid) with no valepotriates, which are normally in the essential oil.^[18] The hops contained 0.479% total flavonoids expressed as rutin equivalents (REs).^[18]

A standardized mix of Valeriana officinalis and hops, called Ze91019, is used as a sleep aid.

NSF-3 is another formulation where 450mg of each serving contains valerian (300mg at 0.8% valerinic acid) and hops (30mg standardized to 0.35% rutin), but also with the addition of true passionflower (passiflora incarnate) at 80mg (4% isovitexin); NSF-3 (450mg) appears to be comparable to 10mg zolpidem in improving sleep quality.^[20]

A mix of Valeriana officinalis, hops and Passiflora incarnata is called NSF-3. Preliminary evidence suggests it is comparable to zolpidem, a prescription medication, for improving sleep.

NSF-3 is another formulation combining valerian with hops that also includes passionflower. It has been shown to be comparable to zolpidem in improving sleep quality in one study.

Another combination formula classified as Ze185 and with the brand name Relaxane® consists of 90mg butterbur (7-14:1 concentration from 90% ethanolic extract), 90mg valerian (5-8:1 concentration from a 55% methanolic extract), 90mg passionflower (3-6:1 concentration from 50% ethanol), and 60mg lemon balm (3.5-5.5:1 concentration from 20% ethanol).^[21]

Valerian at concentrations of 18.75-1875µg/mL does not appear to induce the activity of CYP1A2.^[22] Valerian seems to inhibit CYP2E1. but weakly; even concentrations as high as 1875µg/mL yield only 20% inhibition, so this inhibition is not thought to be physiologically relevant.^[23] Valerian does not seem to influence both CYP1A2 and CYP2E1 activity in humans when taking 125mg taken thrice daily.^[24]

CYP2D6 activity appears to be increased by 20-40% of control in the presence of 18.75-1875µg/mL, a potency comparable in vitro to 50µM rifampicin.^[22] Another study found that valerian induced CYP2C19 activity to a slightly larger degree (57%) in the 18.75-187.5µg/mL range with no appreciable induction at a higher concentration of 1875µg/mL.^[23] Oral ingestion of 125mg valerian root thrice daily has failed to influence human kinetics of CYP2D6^[24] while a higher dose of 1,000mg of valerian (1% valerenic acid) nightly for two weeks mildly inhibited CYP2D6.^[5]

When investigating CYP3A4, valerian extracts showed weak inhibition (IC₅₀ only 9.56% of its full potency), although there appeared to be a large variation in this value(between 3.09%-70.49%).^[25] Elsewhere, CYP3A4 activity in vitro was found to be minorly increased with valerian in the concentration range of 187.5-1875µg/mL with no significant influence at 18.75µg/mL,^[22] but CYP3A4 activity in humans given 125mg of valerian thrice daily for 28 days has failed to find any induction^[24] and no inhibitory nor inductive actions were noted with two weeks nightly ingestion of 1,000mg valerian (1% valerenic acid).^[5]

Valeriana officinalis may interact with other drugs in a moderate way, but strong interactions are unlikely, especially at standard doses.

A 70% ethanolic extract of valerian roots (containing more than 0.1% valerenic acids) appears to have weak inhibitory activity on UGT1A4 (IC₅₀ of 406.5+/-35.3µM) with no detectable inhibitory activity on either UGT1A6 or UGT1A9 at concentrations under 1mg/mL.^[26]

Valeriana officinalis may have a weak inhibiting effect on some enzymes in sulfation. The practical signifiance of this pathway in regard to oral supplementation is not clear at this time. Significant interaction, however, is doubtful.

Methanolic extracts of valerian root have failed to show any glutaminergic activity (assessed by neuronal activity) at concentrations up to 50µg/mL, a concentration which does show serotonergic effects^[27] although a the valerenic acid and isoborneol extracted from valerian in water is known to modify glutamate binding in vitro.^[6]

When looking at valerenic acid alone, it appears that 800ng/mL can increase glutamate binding in the presence of quinic acid by up to 49% while isoborneol suppresses it at this concentration by 14% yet increased glutamate binding in the presence of L-AP4 a metabotropic glutamate receptor III agonist.^[6] It appears that metabotropic glutamate receptors, specifically mGluR groups I and II, may mediate some of the anxiolytic properties of valerian and isolated valerenic acid in zebrafish,^[28] as glutamate signalling,^[29] specifically group I and II mGluRs, may be anxiolytic when activated.^[30]

Several compounds in Valeriana officinalis may interact with metabotropic glutamate receptors. These interactions may be related to the anti-anxiety properties of valerian, though further research is needed to determine the exact mechanism involved.

Compounds in valerian may interact with metabotropic glutamate receptors, although isoborneal and valerenic acid show opposing actions. These interactions may be related to anxiolytic properties of valerian, although the exact manner of interaction (either direct of via modifying the actions of other ligands) is not yet known.

Valerian appears to be a positive modulator of GABA_A receptors,^[31] acting in a concentration-dependent manner on a site different from the GABA binding site^[31] and enhancing GABA_A neurotransmission, which is thought to underlie most of valerian's effects.^[32] This particular effect can be traced back to valerenic acid in particular binding to the β3 subunit of the GABA_A receptor,^[33] since deleting this subunit out of mouse receptors blocks interactions with valerenic acid^[34]), and depleting valerian of the valerenic acid content seems to be associated with no detectable GABAergic signalling.^[35]

Derivatives of valerenic acid, notably acetoxyvalerenic acid, can also bind to this receptor without appreciable potentiation of the receptor^[33] and may block the actions of valerenic acid,^[35] whereas hydroxyvalerenic acid seems not to influence the receptor^[33] and can displace valerenic acid from its binding site.^[34] Hydroxyvalerenic acid seems to be less inhibitory than acetoxyvalerenic acid, since valerian extracts containin the latter have more effect on the receptor than fractions containing the former.^[35]

Extracts of Valeriana officinalis appear to enhance the signalling of gamma-aminobutryic acid (GABA) when tested in vitro. GABA is one of the main sedative neurotransmitters.

When measuring the 50-100% methanolic extracts, there was no determinable binding to the GABA_A receptor^[27] and all lignans do not have direct activity,^[7] but one lignan (pinoresinol-4,4'-di-β-d-glucoside) enhanced GABA_A signalling by 23% at 10µM.^[7] 6-Methylapigenin, found in valerian,^[10] is also known to increase GABA_A signalling in the presence of agonists^[36] such as hesperidin (found in valerian in low levels, and an agonist when administered as an injection at 2-4mg/kg^[10]) or linarin (also a sedative when injected^[11]). It is not known what role these compounds play in valerian extracts' purported therapeutic effects, since depleting the extracts of valerenic acid seems sufficient to ablate GABAergic signalling in vitro.^[35]

The ligands and flavonoids in Valeriana officinalis appear to enhance GABA signalling at higher-than-expected concentrations during oral supplementation. Practical significance of this enhancement for humans is not yet known, but the effects of the ligands and flavonoids is less relevant to GABAergic signalling than valerenic acid is.

It is unsure whether or not the GABAergic system is relevant to oral supplementation of valerian, as it has been noted that valerian has failed to augment the effects of alcohol^[37] which should occur with anything that potentiates GABAergic signalling (such as Ashwagandha).

Significant GABAergic signalling after oral ingestion in humans has not been observed, despite it potentially underlying the two biggest benefits of Valeriana officinalis: sleep enhancement and anti-anxiety effects.

Valerian methanolic extract (35%) has been noted to displace LSD (a ligand to some serotonin receptors) from the 5-HT₆ receptor by by 12-13% at 10-100µg/mL, and the higher tested concentration (100µg/mL) is able to displace LSD from binding to the 5-HT₇ receptor by 11% and the 5-HT_4E receptor by 31%.^[18] That being said, reliable IC₅₀ values were not obtained in vitro up to 1000µg/mL,^[18] and elsewhere the interaction with the 5-HT₆ and 5-HT₇ receptors have failed to be replicated with the 50-100% methanolic extracts.^[27]

No known interaction occurs with 5-HT_1A, 5-HT_1B, 5-HT_2C, or 5-HT₃ receptor subsets with the basic extract^[27] and all lignans have failed to influence 5-HT_1A signalling;^[7] there appears to have weak binding affinity to the 5-HT_2B receptor, with 51% binding at 50µg/mL.^[27]

The 5-HT_5A receptor appears to have affinity for the methanolic extracts of valerian and valerenic acid, with the former having agonistic properties on this receptor with 80% binding at 50µg/mL^[27] and the latter appears to have partial agonist properties with an IC₅₀ of 17.2µM (K_i of 10.7µM).^[27]

Though components of valerian extract appear to associate with some serotonin receptors when present in moderate to high concentrations, specific molecules have not been isolated yet and further study is needed to understand the effect of Valeriana officinalis on the serotonin system.

One study in vitro noted binding affinity to the serotonin transporter, with 53% binding affinity at 50µg/mL.^[27]

Valerian methanolic extracts do not appear to have any affinity for dopamine receptors (D1, D2, D3, D4.4, and D5) nor the dopamine transporter up to 100µg/mL.^[18]

No significant interactions have been noted between dopamine receptors and Valeriana officinalis.

A valerian methanolic extract at 100µg/mL appears to have affinity for the ML2 receptor by displacing the ligand (iodomelatonin) by 56%, although 10µg/mL was ineffective and there were no associations with the ML1 receptor or the melanin concentrating hormone (MCH) receptor,^[18] the latter being linked to sleep disorders.^[38] The IC₅₀ in regards to displacing the ligand on ML2 was determined to be 74µg/mL, while interactions with ML1 required 450µg/mL to reach the IC₅₀ value, both being less than the reference compound of melatonin (122nM and 170pM for ML2 and ML1, respectively).^[18]

Interactions with the melatonin receptors have failed to occur elsewhere with up to 50µg/mL of the 50-100% methanolic extracts, or with petroleum or dichloromethane extracts.^[27]

Interactions between Valeriana officinalis and melatonin signalling have been noted in vitro, but these interactions are very weak and most likely not relevant to oral supplementation.

The olivil lignan in valerian known as 4'-O-β-d-glucosyl-9-O-(6"-deoxysaccharosyl)olivil appears to be an A1 receptor ligand, and exerts 80+/-5% affinity at 100μM and initially thought to have a K_i of 5.28+/-0.68μM;^[7] when investigating further, it appears that this lignan had a K_i of 23.6-31μM for the low affinity state (26nM for high affinity without GTP), and due to having an EC₅₀ value of 3.98+/-0.42μM it was deemed a partial agonist.^[7] This affinity has been replicated elsewhere in the range of 150-190µM (EC₅₀ in activating the receptor between 850-900µM), which was comparable to hops (130µM); the compound formulation of the two (Ze91019) did not appear to be synergistic.^[19] Incubation of neurons with valerian extracts appears to suppress A1 siganlling in a concentration dependent manner up to 10mg/mL.^[39]

Affinity to the A2A receptors are poor with the aforementioned lignan^[7] and valerian extracts in general.^[19]

Adenosine signalling is not practically relevant in regard to oral supplementation of Valeriana officinalis, even though water extracts of valerian is able to signal through A1 receptors, and a lignan from the root has been confirmed to be a partial A1 agonist. These effects are found at an impractically high concetration.

The water extract of valerian appears to be able to signal through A1 receptors, and a lignan from the roots has been confirmed to being a partial A1 agonist. The concentrations at which these act appreciably are high, and due to the concentration of these lignans in valerian being low it is thought that adenosine signalling is not practically relevant to oral supplementation of valerian.

It appears that the anti-epileptic properties of the valerian water extract (roots at 200-800mg/kg injections) in amygdala-kindled rats is partially aborgated by A1 receptor antagonism, suggesting signalling through this receptor.^[40]

Injections of Valeriana officinalis, administed to rats, appear to cause adenosinergic signalling. The injected dose must be very high to achieve this effect.

Adenosinergic signalling appears to be implicated following injections of Valeriana officinalis in rats, but the dose injected is very high.

Valerian has been noted to have affinity for the neuropeptide 1 (NPY₁) receptor and displaces the ligand by 11-13% at the concentration range of 10-100µg/mL, with no apparent associated with NPY₂.^[18]

The effect of Valeriana officinalis supplementation on appetite has not been studied yet, but valerian does have an affinity for receptors involved in appetite regulation.

In amygdala-kindled rats (known to experience anticonvulsive effects from A1 but not A2A adenosine receptor activation^[41][42]), injections of the water extract of valerian root at 500-800mg/kg (but not 200mg/kg) is able to exert anticonvulsive effects in a manner that is partially blocked with an A1 receptor antagonist.^[40] Oddly, the petroleum ether extract (50-100mg/kg) had proconvulsive effects.^[40]

Large injections of Valeriana officinalis may have anti-epileptic effects, related to adenosinergic neutronasmission. This does not apply to oral supplementation.

Any possible anti-epileptic effects seem to be related to adenosinergic neurotranmission by mimicking adenosine signalling on the A1 receptor, although this may require large injections of valerian and not apply to oral supplementation.

The root of valerian has traditionally been used to treat anxiety^[43] which is thought to be due to valerenic acid potentiating GABA_A receptors,^[34][44] a property not shared with its derivaties hydroxyvalerenic acid and acetoxyvalerenic acid despite all three binding to the same site on GABA_A receptors (β3).^[34][33]

It has been noted in a rat study that when given a controlled amount of total acids (0.5-2.0mg/kg), those with a higher valerenic acid content relative to acetoxyvalerenic acid (12:1) exerted anxiolytic benefits at the lower dose whereas a higher dose (2.0mg/kg) was required for the 1:1.5 ratio.^[44]

Valerenic acid is able to bind to GABA_A receptors increase the strength of their signalling. This is thought to underlie the anti-axiety effects of Valeriana officinalis.

The ability of valerenic acid to bind to GABA_A receptors and potentiate their signalling is thought to underlie anxiolytic properties

One human study in generalized anxiety disorder (GAD) using valerian valepotriates at 81.3mg daily for four weeks and assessing symptoms by HAM-A and STAI-Trait rating scales (as well as self report) failed to find a significant benefit with the valepotriates relative to placebo or the reference drug (diazepam).^[45]

Preliminary human evidence has failed to find any benefit associated with Valeriana officinalis for the treatment of generalized anxiety disorder.

The first pilot studies of eight persons with valerian noted that it was able to improve sleep latency (the time required to fall asleep) assessed by wrist activity measurement; 450mg of the extract performed similarly to 900mg, but the larger dose was associated with drowsiness the following day and only the lower dose was associated with subjective reports of better sleep latency.^[17] This study appeared to set the stage for dosing (450mg) in studies on sleep latency in otherwise healthy persons, logically extending to persons with insomnia (the population that would benefit most from valerian interventions).

A meta-analysis on valerian and insomnia^[14] assessed sleep latency. Of the ten trials that qualified for the analysis(nine located online^{[46][47][48][49][50][51][52][53][54]}), the analysis found a statistically insignificant effect of a 0.7 minute decrease in sleep latency time.^[14] Subgroup analysis based on study quality (Jadad rating) and excluding select studies from analysis also failed to procure significant results,^[14] and the two studies showing the most magnitude in reducing sleep latency^[47][52] both crossed the zero point and were statistically insignificant.

A meta-analysis of sleep latency has failed to find significant benefits associated with Valeriana officinalis.

When looking at rodent research, flavonoids such as linarin appear to enhance phenobarbital-induced sleep time when injected (7-14mg/kg),^[11] while valerenic acid^[11] and 6-methylapigenin are inherently inactive^[11][10] but can enhance the activity of other flavonoids when co-administered.^[10][11] The combination of linarin (4mg/kg) and valerenic acid (5mg/kg) injected into rats appears to be most effective.^[11]

Rats injected with isolated flavonoids from Valeriana officinalis may experience longer sleep. This effect may come from directly activated gamma-aminobutyric acid (GABAergic signalling), or through Valeriana officinalis stimulating the activity of other endogenous and exogenous agents, which, in turn, incraese GABAergic signalling.

Isolated flavonoids form valerian may enhance sleep time when injected into rats by either directly activating GABAergic signalling or enhancing the activity of other agents (endogenous or exogenous) that increase GABAergic signalling

Research reviews on the topic of valerian and sleep quality have initially reported a benefit associated with valerian in improving sleep quality (RR of 1.8 and 95% CI of 1.2-2.9)^[55] with other reviews being unable to find benefits based on the evidence at the time.^[56][57] The most recent meta-analysis to date assessing trials in the aforementioned reviews plus new trials (18 in total assessing 1,317 persons)^[14] found no evidence to support an improvement in sleep quality in either healthy persons or those with insomnia as assessed by rating scales and objective sleep measurements (actigraphy); these null results were not associated with any publication bias but were likely due to the fact that many (40%) of the included trials had less-than-ideal methodology, having a Jadad score of less than 3.^[14] When benefit was noted to a significant degree, it was solely on the subjective (yes/no) rating scale of whether persons felt that their sleep was improved: the RR was 1.37 and the 95% CI 1.05-1.78.^[14] Two reviews published on valerian after the publication of this meta-analysis^[58][59] do not overturn its conclusions.

The single meta-analysis related to Valeriana officinalis and sleep quality as compared to placebo has failed to find significant benefit. It should be noted that one parameter was strictly self-reported, based solely on whether a study participant had felt that they had a more restful night's sleep.

Valerian at 750mg (root extract) daily for eight weeks in persons with diagnosed OCD noted a reduction in symptoms assessed by the Y-BOCS (rating scale) prominent after four weeks and to the end of the study ultimately reaching a 10 (out of 40) point reduction, while placebo reached a 5 point reduction. There were no significant differences at two weeks time, and there were no significant side-effects aside from somnolence (sleepiness) which occurred in 53.3% of the valerian subjects yet only 18.75% of the placebo.^[60]

One pilot study has noted that a slightly larger than normal dose of Valeriana officinalis confers benefits for symptoms of OCD, when taken as a daily supplement. The benefits, relative to placebo, were moderate at best.

Supplementation of 100mg/kg valerian root or an equivalent amount of valerenic acid (340μg/kg) for three weeks in rats cognitive aged with D-galactose beforehand appears to improve memory and learning associated with a decrease in corticosterone in serum and a decrease in lipid peroxidation in the hippocampus.^[61]

One study reported that the most common side effect (16% of a sample of 19) was 'vivid dreams' induced by 600mg Valerian extract.^[62]

Oral intake of 100mg/kg of valerian root or an equivalent amount of valerenic acid (340μg/kg) appears to reduce corticosterone levels in the plasma of aged rats.^[61]

Sleep disorders during cancer therapies appear to be significantly larger than in the standard population, with prevalence estimates ranging between 23%–61%.^[63][64][65] As sleep is a major determinant of quality of life in this cohort,^[66] improving sleep during cancer therapy is desirable and valerian is of interest due to its relatively safe history of usage as a dietary supplement.

Supplementation of valerian root (450mg with 0.8% valerenic acid an hour before bed) for eight weeks in persons undergoing cancer therapy (not limited to one cancer nor type of therapy) was able to beneficially influence the time required to fall asleep relative to placebo and reduced reports of disturbed sleep from 84% (placebo) down to 60%.^[15] While there was no benefit to sleep seen on the PSQI, there were reductions in self-reported fatigue as assessed by the BFI and POMS when using valerian, without any reported drowsiness.^[15]

Cancer patients taking Valeriana officinalis appear to experience less impaired sleep, but this does not occur alongside improvements in sleep quality per se.

Dysmenorrhea (also known as menstrual cramps) is known to affect 42-72% of women of menstruating age^[67][68][69] and can impair quality of life. Since valarian has been found to have antispasmolytic properties in vitro through activating potassium channels while inhibiting calcium channels^[70] (menstrual pain being spasmodic in nature), it has been investigated as a potential aid to dysmenorrhea.

Supplementation of valerian root at 225mg thrice daily for two menstrual cycles was able to reduce the magnitude of pain as assessed by a 10 point rating scale (73.3% reduction; from 7.45 to 1.99) to a greater degree than placebo (37.6%; from 7.06 to 4.41) while valerian also reduced self-reported duration of pain.^[71]

Valeriana officinalis supplementation has been associated with reduced abdonimal pain from menstruation.

Valerian is sometimes recommended for menopausal symtoms mostly pertaining to sleep and anxiety, and one trial using supplementation of valerian (225mg of the root extract thrice daily for eight weeks) noted that supplementation was able to reduce hot flash frequency and severity by 29.3% after 4 weeks and 47.5% after 8 weeks.^[72] This study used a custom questionnaire rather than a standardized test.^[72]

One study using 530mg of valerian root twice daily in postmenopausal women reporting insomnia noted that while 4% of the placebo group found benefit, valerian was assocaited with a 30% reduction in reported insomnia as assessed by the PSQI.^[73] Another study has assessed valerian and its effects on sleep after menopause, noting benefits relative to placebo (also assessed by PSQI). However, in this study, valerian (160mg) was combined with lemon balm (80mg).^[74]

Researchers in one study have observed benefits for sleep in menopausal women when supplementing Valeriana officinalis. However, these results are at odds with the usual effects of Valeriana officinalis, and should be taken with a grain of salt.

In addition for use in cognitve protection, Licorice (Glycyrrhiza species) is traditionally used to enhance absorption of other herbal bioactives.

25mg/kg of a licorice extract (from glycyrrhiza glabra) alongside 50mg/kg of valerian root in mice appears to potentiate the anxiolytic properties of valerian when consumed at subactive doses despite itself being inactive.^[75]

Preliminary evidence suggests that licorice enhances the anti-anxiety properties of Valeriana officinalis.

Valerian is generally regarded as highly safe, with few side-effects reported to be significantly different than placebo. A meta-analysis noted a significant increase in rates of diarrhea ^[14] and while drowsiness is sometimes reported as a side-effect with night-time dosing^[60] this it not always the case in isolated trials^[76][15] nor a meta-analysis of side-effects.^[14]

Side-effects of drowsiness during the day tend to be reported when valerian is taken at higher doses that require daytime dosing (e.g. 450mg thrice a day), and while the 'hangover' effect does not tend to occur with 450mg of the supplement before sleep it has been noted with 900mg.^[17]

Valeriana officinalis supplementation at the recommended dose is very safe. Higher than normal doses can cause drowsiness.

Valerian root has been implicated in a case of hyponatremia (low blood sodium) in a psychiatric patient who consumed an excess (3.5L) of valerian-containing beverages purported to reduce anxiety, although it was thought that excess water intake was the main factor in this case of hyponatremia.^[77]