What is Valerian

Valerian also known as Valeriana officinalis L., setwall (English), Valerianae radix (Latin), Baldrianwurzel (German) or phu (Greek), is a member of the Valerianaceae family, a perennial plant native to Europe and Asia and naturalized in North America ¹. Valeriana officinalis has a distinctive odor that many find unpleasant ². There are over 250 Valerian species worldwide, including Valeriana wallichii DC., Valeriana edulis Nutt., and Valeriana fauriei Briq., among which Valeriana officinalis L. is the most well known in United States and Europe as “valerian.” In the United States, valerian is regulated by the Food and Drug Administration (FDA) as a dietary supplement used as a sleep aid ³. According to the European Medicine Agency (European equivalent to the FDA), the well-established uses of Valeriana officinalis root include the relief of mild symptoms of mental stress and to aid sleep ⁴. For relief of nervous tension, recommended Valerian (Valeriana officinalis) oral dosages are 400-600 mg dry hydroalcoholic extract or comminuted herbal substance (root) 0.3-3 g up to 3 times daily ⁵. Valerian is considered relatively safe and well-tolerated, however the European Medicine Agency 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 ⁵. Because it is possible (though not proven) that valerian might have a sleep-inducing effect, it should not be taken along with alcohol or sedatives.

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 ⁶, which analyzed 9 randomized clinical trials, found contradictory results and significant inconsistency in terms of patients, experimental design and methodology among the trials. Another systematic review and meta-analysis published in 2006 ⁷, analyzed 16 studies and this study also found significant methodological problems. Taibi et al. ⁸ conducted a systematic review on 37 studies, of which 29 were controlled trials and 8 were open-label trials. They concluded that, although valeriana officinalis is a safe herb, evidence did not support the clinical efficacy of valerian as a sleep aid for insomnia ⁸. A meta-analysis of 18 randomized placebo-controlled trials published in 2010 ⁹, concluded that valerian’s effectiveness had not been demonstrated with quantitative or objective measures although valerian could improve subjective sleep quality. 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 ³. In the American Academy of Sleep Medicine 2017 clinical practice guidelines, it recommended against using valerian for chronic insomnia in adults ¹⁰.

Research suggests that valerian is generally safe for short-term use by most adults. It has been used with apparent safety in studies lasting up to 28 days. The safety of long-term use of valerian is unknown. Little is known about whether it’s safe to use valerian during pregnancy or while breastfeeding.

Side effects of valerian include headache, stomach upset, mental dullness, excitability, uneasiness, heart disturbances, and even insomnia in some people. A few people feel drowsy in the morning after taking valerian, especially at higher doses. Some people experience dry mouth or vivid dreams.

Valerian supplement

Preparations of valerian marketed as dietary supplements are made from Valeriana officinalis roots, rhizomes (underground stems), and stolons (horizontal stems). Dried valerian roots are prepared as teas or tinctures, and dried plant materials and extracts are put into capsules or incorporated into tablets ¹¹.

There is no scientific agreement as to the active constituents of valerian and its activity may result from interactions among multiple constituents rather than any one compound or class of compounds ¹². The content of volatile oils, including valerenic acids; the less volatile sesquiterpenes or the valepotriates (esters of short-chain fatty acids) is sometimes used to standardize valerian extracts. As with most herbal preparations, many other compounds are also present.

Valerian is sometimes combined with other botanicals ¹¹.

How does valerian work?

Although the use of valerian extracts as a sedative and sleep aid dates back to the 18th century and a number of constituents have been identified in the last 120 years ¹³, it is not known which may be responsible for its sleep-promoting effects in animals and in vitro (test tube) studies ¹⁴. The identified constituents include iridoids known as valepotriates (valtrate, isovaltrate, didrovaltrate and acevaltrate) ¹⁵, essential oil constituents including monoterpenes (e.g. borneol, bornyl acetate), sesquiterpenes (e.g. valerenal, valerenic acid), and carboxylic compounds (valeric / isovaleric acid) ¹⁶, lignans ¹⁷, flavonoids ¹⁸ and low levels of gamma-aminobutyric acid (GABA) ¹⁹. It is likely that there is no single active compound and that valerian’s effects result from multiple constituents acting independently or synergistically ²⁰. Valeriana edulis (Mexican valerian) and Valeriana wallichii (Indian valerian) contain higher levels of iridoids, while valerenic acid and acetoxyvalerenic acid are unique to Valerian officinalis ²¹.

Two categories of constituents have been proposed as the major source of valerian’s sedative effects. The first category comprises the major constituents of its volatile oil including valerenic acid and its derivatives, which have demonstrated sedative properties in animal studies ²². However, valerian extracts with very little of these components also have sedative properties, making it probable that other components are responsible for these effects or that multiple constituents contribute to them ²³. The second category comprises the iridoids, which include the valepotriates. Valepotriates and their derivatives are active as sedatives in vivo but are unstable and break down during storage or in an aqueous environment, making their activity difficult to assess ²⁴.

Valepotriates are unstable thermolabile compounds that rapidly decompose ³. The characteristic odor of dried valerian is due to isovaleric acid released from decomposing valepotriates ²⁵. Although the mechanistic roles of valepotriates in the therapeutic effects are yet to be clarified, pre-clinical evidence suggests that valepotriates exert anxiolytic ²⁶ and antidepressant-like effects ²⁷, possibly via the dopaminergic and noradrenergic neurotransmission but not via the serotonergic system ²⁷. The monoaminergic neurotransmitters (dopamine, noradrenaline, and serotonin [5-HT]) play overlapping roles in the cause of anxiety and depression, and medications targeting these systems are proved to be effective in treating both anxiety and depression ²⁸. Moreover, waking and sleep states are highly complex processes that are elegantly orchestrated by fine‐tuned neurochemical changes, including the neurotransmitters and neuromodulators glutamate, acetylcholine, gamma‐amino‐butyric acid (GABA, an inhibitory neurotransmitter), noradrenaline (norepinephrine), dopamine, serotonin [5-HT], histamine, hypocretin, melanin concentrating hormone, adenosine, and melatonin ²⁹. Thus, the presence of valepotriates is likely to be essential in treating these disorders. In addition, valtrate reduced the serum glucocorticoid level in a rat anxiety model ³⁰, suggesting hypothalamus-pituitary-adrenal axis (HPA) modulatory potential of valepotriates. Considering the significant association between neuroendocrine-immune axis imbalance and stress vulnerability and resilience ³¹, the potential impact on the hypothalamus-pituitary-adrenal axis is particularly important. Stress can disturb the sleep, and stress reactivity is implicated in vulnerability to insomnia and other stress-related disorders such as anxiety and depression ³². Furthermore, glucocorticoid imbalance could lead to amyloid formation and tau accumulation, hallmarks of Alzheimer’s disease ³³ and elevated glucocorticoid levels are associated with neurodegenerative disorders ³⁴. Sleep problems are associated with a number of comorbidities including anxiety, depression, and dementia in both adulthood ³⁵ and childhood ³⁶. Thus, valepotriates may prevent stress-induced neuropsychiatric disorders including anxiety and depression, as well as cognitive dysfunction, by restoring endocrine-immune balance.

A possible mechanism by which a valerian extract may cause sedation is by increasing the amount of gamma‐amino‐butyric acid (GABA, an inhibitory neurotransmitter) available in the synaptic cleft. Results from an in vitro (test tube) study using synaptosomes suggest that a valerian extract may cause GABA to be released from brain nerve endings and then block GABA from being taken back into nerve cells ³⁷. In addition, valerenic acid inhibits an enzyme that destroys GABA ³⁸. Valerian extracts contain GABA in quantities sufficient to cause a sedative effect, but whether GABA can cross the blood-brain barrier to contribute to valerian’s sedative effects is not known. Glutamine is present in aqueous but not in alcohol extracts and may cross the blood-brain barrier and be converted to GABA ³⁹. Levels of these constituents vary significantly among plants depending on when the plants are harvested, resulting in marked variability in the amounts found in valerian preparations ⁴⁰.

Valerian benefits

In a systematic review of the scientific literature, nine randomized, placebo-controlled, double-blind clinical trials of valerian and sleep disorders were identified and evaluated for evidence of efficacy of valerian as a treatment for insomnia ⁶. Reviewers rated the studies with a standard scoring system to quantify the likelihood of bias inherent in the study design ⁴¹. Although all nine trials had flaws, three earned the highest rating (5 on a scale of 1 to 5) and are described below. Unlike the six lower-rated studies, these three studies described the randomization procedure and blinding method that were used and reported rates of participant withdrawal.

The first study used a repeated-measures design; 128 volunteers were given 400 mg of an aqueous extract of valerian, a commercial preparation containing 60 mg valerian and 30 mg hops, and a placebo ⁴². Participants took each one of the three preparations three times in random order on nine nonconsecutive nights and filled out a questionnaire the morning after each treatment. Compared with the placebo, the valerian extract resulted in a statistically significant subjective improvement in time required to fall asleep (more or less difficult than usual), sleep quality (better or worse than usual), and number of nighttime awakenings (more or less than usual) ⁴². This result was more pronounced in a subgroup of 61 participants who identified themselves as poor sleepers on a questionnaire administered at the beginning of the study ⁴². The commercial preparation did not produce a statistically significant improvement in these three measures. The clinical significance of the use of valerian for insomnia cannot be determined from the results of this study because having insomnia was not a requirement for participation. In addition, the study had a participant withdrawal rate of 22.9%, which may have influenced the results ⁴².

In the second study, eight volunteers with mild insomnia (usually had problems falling asleep) were evaluated for the effect of valerian on sleep latency (defined as the first 5-minute period without movement) ⁴³. Results were based on nighttime motion measured by activity meters worn on the wrist and on responses to questionnaires about sleep quality, latency, depth, and morning sleepiness filled out the morning after each treatment ⁴³. The test samples were 450 or 900 mg of an aqueous valerian extract and a placebo. Each volunteer was randomly assigned to receive one test sample each night, Monday through Thursday, for 3 weeks for a total of 12 nights of evaluation. The 450-mg test sample of valerian extract reduced average sleep latency from about 16 to 9 minutes, which is similar to the activity of prescription benzodiazepine medication (used as a sedative or tranquilizer). No statistically significant shortening of sleep latency was seen with the 900-mg test sample ⁴³. Evaluation of the questionnaires showed a statistically significant improvement in subjectively measured sleep. On a 9-point scale, participants rated sleep latency as 4.3 after the 450-mg test sample and 4.9 after the placebo. The 900-mg test sample increased the sleep improvement but participants noted an increase in sleepiness the next morning. Although statistically significant, this 7-minute reduction in sleep latency and the improvement in subjective sleep rating are probably not clinically significant ⁴³. The small sample size makes it difficult to generalize the results to a broader population.

The third study examined longer-term effects in 121 participants with documented nonorganic insomnia ⁴⁴. Participants received either 600 mg of a standardized commercial preparation of dried valerian root (LI 156, Sedonium) or placebo for 28 days ⁴⁴. Several assessment tools were used to evaluate the effectiveness and tolerance of the interventions, including questionnaires on therapeutic effect (given on days 14 and 28), change in sleep patterns (given on day 28), and changes in sleep quality and well-being (given on days 0, 14, and 28). After 28 days, the group receiving the valerian extract showed a decrease in insomnia symptoms on all the assessment tools compared with the placebo group. The differences in improvement between valerian and placebo increased between the assessments done on days 14 and 28 ⁴⁴.

The reviewers concluded that these nine studies are not sufficient for determining the effectiveness of valerian to treat sleep disorders ⁶. For example, none of the studies checked the success of the blinding, none calculated the sample size necessary for seeing a statistical effect, only one partially controlled prebedtime variables ⁴⁴ and only one validated outcome measures ⁴².

Two other randomized, controlled trials published after the systematic review described above are presented below ⁶:

1. In a randomized, double-blind study, 75 participants with documented nonorganic insomnia were randomly assigned to receive 600 mg of a standardized commercial valerian extract (LI 156) or 10 mg oxazepam (a benzodiazepine medication) for 28 days ⁴⁵. Assessment tools used to evaluate the effectiveness and tolerance of the interventions included validated sleep, mood scale, and anxiety questionnaires as well as sleep rating by a physician (on days 0, 14, and 28) ⁴⁵. Treatment result was determined via a 4-step rating scale at the end of the study (day 28). Both groups had the same improvement in sleep quality but the valerian group reported fewer side effects than did the oxazepam group ⁴⁵. However, this study was designed to show superiority, if any, of valerian over oxazepam and its results cannot be used to show equivalence.
2. In a randomized, double-blind, placebo-controlled crossover study, researchers evaluated sleep parameters with polysomnographic techniques that monitored sleep stages, sleep latency, and total sleep time to objectively measure sleep quality and stages ⁴⁶. Questionnaires were used for subjective measurement of sleep parameters. Sixteen participants with medically documented nonorganic insomnia were randomly assigned to receive either a single dose and a 14-day administration of 600 mg of a standardized commercial preparation of valerian (LI 156) or placebo ⁴⁶. Valerian had no effect on any of the 15 objective or subjective measurements except for a decrease in slow-wave sleep onset (13.5 minutes) compared with placebo (21.3 minutes). During slow-wave sleep, arousability, skeletal muscle tone, heart rate, blood pressure, and respiratory frequency decreased. Increased time spent in slow-wave sleep may decrease insomnia symptoms. However, because all but 1 of the 15 endpoints showed no difference between placebo and valerian, the possibility that the single endpoint showing a difference was the result of chance must be considered ⁴⁶. The valerian group reported fewer adverse events than did the placebo group.

Although the results of some studies suggest that valerian may be useful for insomnia and other sleep disorders, results of other studies do not. Interpretation of these studies is complicated by the fact the studies had small sample sizes, used different amounts and sources of valerian, measured different outcomes, or did not consider potential bias resulting from high participant withdrawal rates. Overall, the evidence from these trials for the sleep-promoting effects of valerian is inconclusive ⁴⁷.

Valerian uses

Valerian has been used as a medicinal herb since at least the time of ancient Greece and Rome. Its therapeutic uses were described by Hippocrates, and in the 2nd century, Galen prescribed valerian for insomnia ⁴⁸. In the 16th century, it was used to treat nervousness, trembling, headaches, and heart palpitations ⁴⁹. In the mid-19th century, valerian was considered a stimulant that caused some of the same complaints it is thought to treat and was generally held in low esteem as a medicinal herb ⁵⁰. During World War 2, it was used in England to relieve the stress of air raids ⁵¹.

In addition to sleep disorders, valerian has been used for gastrointestinal spasms and distress, epileptic seizures, and attention deficit hyperactivity disorder (ADHD). Today, valerian is promoted for insomnia, anxiety, depression, premenstrual syndrome (PMS), menopause symptoms, and headaches. Two small studies suggest that valerian might be helpful for menopausal symptoms, but there is not enough evidence to know for certain ⁵², ⁵³. However, there’s not enough scientific evidence to support the use of valerian for anxiety, depression, premenstrual syndrome, menstrual cramps, stress, or other conditions ⁵⁴.

The evidence on whether valerian is helpful for sleep problems is inconsistent. In the American Academy of Sleep Medicine 2017 clinical practice guidelines, it recommended against using valerian for chronic insomnia in adults ¹⁰.

Valerian dosage

In the United States, valerian is sold as a dietary supplement, and dietary supplements are regulated as foods, not drugs. Therefore, premarket evaluation and approval by the Food and Drug Administration (FDA) are not required unless claims are made for specific disease prevention or treatment. Because dietary supplements are not always tested for manufacturing consistency, the composition may vary considerably between manufacturing lots. Developing effective standardization methods would be desirable. Meanwhile, the usage of whole herbal substances, valerian root or rhizome, rather than extracts, may be the way to obtain optimal efficacy for the time being.

For relief of nervous tension, recommended oral dosages are 400-600 mg dry hydroalcoholic extract of valerian root or comminuted herbal substance (root) 300 mg to 3 g up to 3 times daily ⁵⁵. The typical dosage of valerian is 300 to 600 mg at bedtime for sleep or taken 3 times daily for stress.

This study ³ demonstrated that valerian could be a safe and useful herb alone and also in combination in treating sleep problems, anxiety, and associated comorbidities. Repeated treatments with the whole valerian root or rhizome consistently promoted sleep quality at 450-1410 mg per day for 4-8 weeks, whereas valerian extracts 300-600 mg per day for 5 days-4 weeks resulted in inconsistent outcomes ³. Evidence is poor with respect to the effectiveness of single valerian dose intervention as a sleep aid.

Valerian side effects

Side effects have been reported with valerian root. These include nausea and abdominal cramps. Headaches, dizziness, itch and gastrointestinal disturbances are the most common effects reported in clinical trials but similar effects were also reported for the placebo ⁴⁶. In one study an increase in sleepiness was noted the morning after 900 mg of valerian was taken ⁴³. Investigators from another study concluded that 600 mg of valerian (LI 156) did not have a clinically significant effect on reaction time, alertness, and concentration the morning after ingestion ⁵⁶. Several case reports described adverse effects, but in one case where suicide was attempted with a massive overdose it is not possible to clearly attribute the symptoms to valerian ⁵⁷.

Patients with open wounds, skin problems, high fever, severe infections and severe heart and circulation problems should not have baths with valerian root medicines. Valerian has been linked to rare instances of clinically apparent liver injury ⁵⁸.

Few adverse events attributable to valerian have been reported for clinical study participants.

Valepotriates, which are a component of valerian but are not necessarily present in commercial preparations, had cytotoxic activity in vitro (test tube study) but were not carcinogenic in animal studies ⁵⁹.

Who should not take valerian?

• Women who are pregnant or nursing should not take valerian without medical advice because the possible risks to the fetus or infant have not been evaluated ⁶⁰.
• Children younger than 3 years old should not take valerian because the possible risks to children of this age have not been evaluated ⁶⁰.
• Individuals taking valerian should be aware of the theoretical possibility of additive sedative effects from alcohol or sedative drugs, such as barbiturates and benzodiazepines ⁶¹.

Valerian interaction with drugs or supplements

Valerian might have additive therapeutic and adverse effects if taken with sedatives, other medications, or certain herbs and dietary supplements with sedative properties. These include the following:

• Benzodiazepines such as Xanax, Valium, Ativan and Halcion.
• Barbiturates or central nervous system depressants such as phenobarbital (Luminal), morphine, and propofol (Diprivan).
• Dietary supplements such as St. John’s wort, kava, and melatonin.

Individuals taking these medications or supplements should discuss the use of valerian with their healthcare providers.

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