VALERIAN: Valeriana officinalis

Valerian (Valeriana officinalis L.) is a mild sedative and sleep aid that has been popularly used in Europe for several hundred years. Interest in the use of the plant has dramatically increased over the past 20 years, resulting in over 200 scientific papers on its chemistry, pharmacology and clinical applications. Given its long-standing popularity and history of safe use, current interest in the use of valerian preparations continues to grow.

Botany and Nomenclature

Valerian (Valeriana officinalis L.) is a highly variable member of the Valerian family (Valerianaceae) occurring in eastern, southeastern and east-central Europe, extending to south Sweden and the southern Alps. It is locally naturalized westward in Europe (Ockendon, 1976). Valerian was brought to North America by colonists at an early date. It escaped from ,cultivation, becoming naturalized from Nova Scotia to Pennsylvania; Ohio to Minnesota and Quebec (Fernald, 1950). The genus Valeriana includes upwards of 250 species of the northern temperate zone, South Africa and the Andes. Twenty species are indigenous to Europe (Mabberly, 1987). In North America (exclusive of Mexico) there are sixteen native or naturalized species, with five subspecies and two varieties.

Linnaeus noted that the plant is named in honor of Publius Aurelius Licinus Valerianus, Roman emperor from 253-260. The name "valerian" is also attributed to the Latin "valere" meaning "to be in health." (Fernald, 1950).

History

The first century Greek physician Dioscorides and his contemporaries wrote about Valerian as Phu, a name, which incidentally has the same word-root as our colloquial one-word exclamation "pew." The plant was rightly named in that context, as there are few roots with such a distinctive odor -- at once perfume-aromatic, or to the olfactory organs of most, offensive in odor. Not to cats, though, for as with catnip and perhaps even more so, felines are attracted to the aromatic root. Cats are reported to have attempted to gain access to the herb by scratching through the labels of apothecary jars. The eighteenth century English physician, William Cullen, suggested that the quality of the valerian of apothecary's shops could be determined by how cats react to it. (Cullen, 1808).

Initial publication of the word valerian comes in recipes of the Anglo-Saxon leech books of the eleventh century. The word Valeriana is believed to have first been used sometime in the ninth or tenth centuries. The 1633 Thomas Johnson edition of Gerarde's Herball gives the old English name as Setwall which he notes is more properly applied to the herb Zedoary (Flückiger and Hanbury, 1879).

Valerian has been used as a flavoring as well as a medicinal herb. Among poor people of Northern England, Gerarde finds it "in such veneration amongst them, that no broths, pottage, or phsyciall meats are worth any thing, if Setwall were not at an end...."

Valerian was not a major medicinal plant of the ancient classical authors, being best known as a diuretic and emmenagogue. The second century Greek physician Galen affirmed he had used it in the treatment of epilepsy of children and adults. The Italian nobleman Fabio Colonna, born in 1567, suffering from birth with epilepsy without relief from his physicians, is said to have searched the classics for a cure. Finding mention of the use of valerian for epilepsy, he took the powdered root in half-spoonful doses, and was eventually completely restored to health. Colonna (also known as Fabius Columna) became an important sixteenth century botanical author. It was his vaunting of the virtues of valerian in the treatment of his own long-standing case of epilepsy that initially generated interest in the plant over the next five centuries (Duncan, 1789; Thornton, 1814; Eberle, 1834; Stille, 1874).

By the late 1700s many writers began to question efficacy of valerian in epilepsy. Cullen (1808) comments that it had been held in esteem for epilepsy since the time of Fabius Columna and "it has been since much taken notice of and employed in practice, frequently with success, but frequently also, particularly in my own practice, without any effect at all. The later circumstance, however, I impute to this, that the best remedies may often fail in a disease which depends upon a diversity of causes; and partly to this, that the valerian is frequently employed in an improper condition" (Cullen, 1808 Vol. 2, p. 213).

The value of valerian as an antispasmodic and sleep aid evolved out of seventeenth and eighteenth century usage. "Its antispasmodic powers in general are very well established: and I trust to many of the reports that have been given of its efficacy," wrote Cullen. Duncan found it to be "useful in procuring sleep, particularly in fever, even when opium fails. But it is principally useful in affections of the hysterical kind" (Duncan, 1789, p. 300). It should be noted that "hysterical fits" of this time period are not to be interpreted by modern definitions of hysteria. Rather, it refers to "fits of the mother" or "womb-sickness" -- conditions related to dysfunction of the ystera or uterus (Cole, 1655).

By the late nineteenth century, uses of valerian preparations had evolved to their modern applications "to quiet nervous excitement, as in hysteria or nervous headache, or to promote sleep in cases of hypochondriasis or nervous restlessness" (Edes, 1882).

Valerian was an official remedy in the United States Pharmacopoeia from 18201936, and official in the National Formulary from 1888-1946.

Modern Use

Valerian is widely used in Europe as a mild nerve sedative and sleep aid for insomnia, excitability, and exhaustion. It has depressant activities on the central nervous system, is antispasmodic, and has been described as having equalizing effects -- acting as a sedative in agitated states and a stimulant in fatigue (Leung and Foster, 1996; Tyler, 1993; Williamson and Evans, 1988). Long-standing clinical experience has provided ample evidence of the value of valerian as a sedative. Discrepancies in results are due to variations in dosage, as well as quality of commercial preparations (Tyler, 1993; Weiss, 1988).

Tincture of valerian presents clinical results only if given in sufficient dosages. Efficacy is not achieved with dosages of 10-20 drops of the tincture. According to Weiss, a whole teaspoonful of tincture is needed to produce satisfactory sedative, spasmolytic (relieving smooth muscle spasms), and sleep-inducing effects. If necessary, it should be given several times daily, or repeated a number of times at 15-30 minute intervals, to achieve expected results in states of acute restlessness. He also notes, that over-dosage is highly unlikely, even in large doses (Weiss, 1988).

The sedative action of valerian has been attributed to a number of chemical fractions or components. A group of unstable compounds known as valepotriates, and some of their degradation products, have been shown to possess sedative activity. Other constituents with sedative activity include components of the essential oil such as valerenic acid and valerenone. Hazelhoff et al. 1979 suggest that there is an interaction between these constituents. Valerian, valerenic acid and the esters of eugenyl and isoeugenyl are spasmolytic (Hendriks et al., 1981).

However, a study by Krieglstein and Grusla (1988) suggests that while valerian definitely contains central nervous system (CNS) depressant compounds, they do not correspond to those that have previously been discussed as the active components. The researchers report that valepotriates, valerenic acid, valeranone and the volatile oil of valerian were ineffective as CNS depressant agents when tested individually. An as yet uncharacterized chemical fraction was proposed as the active substance. Isolation or determination of the proposed active chemical fraction was not presented in the article.

A spasmolytic or relaxing effect on the smooth muscle system has been established for the valepotriates and other components of valerian. Therefore, Krieglstein and Grusla evaluated the pharmacological influence of valerian components on the effect on cerebral blood supply as well as cerebral glucose turnover, as parameters for determining the effect of the components on the central nervous system. Fourteen different chemical fractions and pure compounds were evaluated. An increase or decrease of neuron activity in the brain corresponds with a stimulation or depression of neuron activity. According to the authors, the test method used in the study is considered the safest and best qualitative and quantitative technique for measuring neuronal activity. However, the method does not differentiate direct or indirect effects of the substance being tested.

One isolated chemical fraction, termed "fraction 11," and an extract of valerian were shown to coordinate with the central nervous system depressant activity of valerian. Fraction 11 differed very little from other components in thin layer chromatographic patterns. The authors hope to elucidate the fractionated active component in a future publication. A possible mechanism of action may relate to the interaction of valerian constituents with the metabolism of gamma-aminobutyric acid in the brain (ESCOP, 1990). It should be noted that the testing procedures used by Krieglstein and Grusla do not rule out a synergistic effect of several components working in concert to produce the observed sedative effects established for valerian.

The question as to whether the pharmacological and therapeutic activity of botanical preparations results from a single chemical component, or a complex interaction of numerous compounds, again raises its head. The sedative activity of valerian appears, at least for the present, to result from a combination of direct relaxation of the smooth muscle and a depression of some centers of the central nervous system. Active components may involve various chemicals in the essential oil, one or more of the valepotriates, and the as yet unidentified water-soluble fractions noted by Krieglstein and Grusla (Houghton, 1988; Hobbs, 1989).

After the discovery of the valepotriates in the mid-1960s, and pharmacological studies of the early 1970s which attributed spasmolytic, sedative, and anti-convulsant activity to these compounds, many European valerian products were standardized to valepotriates (Hobbs, 1989). But obviously their discovery did not solve the challenge of determining the active components of valerian given the research findings of Krieglstein and Grusla (1988).

The German physician Rudolf Fritz Weiss puts the conflicting information into proper context: "Considerable difficulties arise when plant chemistry and pharmacology are applied to a medicinal plant on the one hand, and to the use and value of such a plant in practice on the other. These difficulties often seem insurmountable, particularly with a plant such as valerian where the actions are mainly in the mental sphere, so that animal experiments yield no convincing evidence, or at least none that will easily transfer to man. The valerian issue is therefore still very much under discussion" (Weiss, 1988, p. 283).

Scientific evaluation of valerian is further complicated by the relatively small number of published clinical studies. An Italian study by Delsignore et al. (1980) involved 40 patients with minor anxiety and emotional tension disturbances. They were randomized into two groups. Twenty patients received two 50 mg. Valerian tablets three times daily, while the other group received placebo. After 21 days, it was determined that valerian was statistically superior, and the absence of side effects confirmed its safety and efficacy in the treatment of emotional tension disturbances.

In the 1980s, P.D. Leathwood, F. Chauffard and other workers of a Nestlé research group published a number of clinical studies on the effects of valerian water extracts on sleep patterns. Valepotriates were absent from the preparations. Sleep quality was subjectively measured by the patient, and confirmed to some extent by EEG. The time taken to fall asleep was reduced, especially in older patients and insomniacs. Dream recall and nocturnal movement were apparently not effected. No drowsiness was reported the following morning (Chauffard et al., 1982; Leathwood, et al. 1982; Leathwood and Chauffard, 1983; Williamson and Evans, 1988; Hobbs, 1989).

In one study (Leathwood et al. 1982) 128 volunteers reported subjective improvements in ratings for sleep quality and the time it took to fall asleep (sleep latency), but without producing a "hangover-like" effect, which is a common complaint of users of synthetic sedative drugs. In the study those who reported that they were habitually poor sleepers, or who took a long time to fall asleep, had the best results. Several authors have noted that one of the most appealing aspects of valerian as a sedative is that it does not interact with alcohol, as do barbiturates, and does not leave the user with a "hangover" in the morning. The authors conducted additional studies, with the ultimate conclusion that the extracts helped to significantly improve sleep quality of those suffering from mild insomnia, with minimal side effects.

Leathwood and Chauffard (1984) conducted a double-blind, randomized study which subjectively assessed sleep ratings. Movements were recorded throughout the night with wrist-worn activity meters. There was a significant decrease in sleep latency with dosages of 450 mg. of valerian compared to placebo. Doubling the dose produced no further improvement in sleep latency. A statistically insignificant number of patients (only eight) were involved in the study.

Safety

Cytotoxicity (cell attacking or destroying activity) and mutagenicity (mutation-causing activity) in animals cells has been reported for valepotriates, and, as a result, they have been studied (without positive results) as antitumor agents. The laboratory studies confirming cytotoxicity of valepotriates has aroused concern about the long-term safety of valerian preparations. Future formulations may be required to contain lower levels of valepotriates (Houghton, 1988). These studies have involved injectable forms of valerian, not oral dosages. Valeriana officinalis preparations are considered safe despite the known in vitro cytotoxic activity of valepotriates (ESCOP 1990). Acute side effects have not been reported. A study by Tufik, et al. (1984) examined the effects of valepotriates in female rats and their offspring. Oral dosage administration for a 30 day period did not produce changes in the average length of the estral cycle, nor the number of estrous phases and was deemed innocuous to pregnant rats and their offspring. For further information see: Houghton, 1988; Weiss, 1988; Hobbs, 1989; ESCOP, 1990; and Blumenthal, et al., 1996.

Valerian is approved as a GRAS (generally recognized as safe) food ingredient in the United States. Extracts and the essential oil are used as flavoring components in alcoholic and nonalcoholic beverages, frozen dairy desserts, candy, baked goods, gelatins, puddings and meat products at an average maximum level of 0.01 percent (Leung and Foster, 1996).

In Germany a Commission E phytomedicine monograph (December, 1986) allows use of valerian in sedative and sleep-inducing preparations for states of excitation, and difficulty in falling asleep due to nervousness. (Blumenthal, et al., 1996.)

Summary

Used for over 1,000 years, valerian extracts are now among the most popular sleep aids of Europe. Traditionally, valerian has been used to relieve muscle spasms, as a mild sedative, treatment for insomnia, hysteria, nervous tension, fatigue, and menstrual cramps. Over the past twenty or thirty years, well over 200 scientific studies on the active chemical components and their effects have been published in the scientific literature, especially in Europe. Experimental data indicates a rational scientific basis for mild sedative qualities, and spasmolytic activity. Additional studies suggest an ability to increase coronary blood flow, as well as mild paid-relieving qualities. Over 120 chemical components have been identified from the root and its essential oil. Questions remain as to the exact nature of active chemical components or fractions, and their specific pharmacological effects and mechanism of action. Despite the remaining questions, overwhelming evidence and clinical experience confirm the sedative effect of alcoholic extracts made from the fresh roots of Valeriana officinalis.

References

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American Botanical Council.

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By Steven Foster

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