Special Feature
Valerian Root for Insomnia
By Mary L. Hardy, MD
The specter of another sleepless night often drives patients to try their favorite sleep remedies-everything from hot milk to hot toddies. Fearful of adverse side effects or the risk of dependency from pharmaceutical "sleeping pills," patients have been trying "natural remedies" in growing numbers. Valerian root extract (VRE) has been a popular herbal sedative since the 19th century.
History/Folklore
A historical record of the medicinal use of valerian dates to Hippocrates, Galen, and Discorides. Although not a major medicinal plant in the Greek pharmacopoeia, valerian was valued as a bitter compound with digestive and diuretic uses. Its aroma was described as pleasant by these authors and it was often included in perfumes-certainly not the case for today's users who often complain about the pungent, "dirty socks" odor of valerian. It is noted as one of the nine herbs of virtue in the Anglo-Saxon physician or healing books of the 10th and 11th centuries. Chaucer mentioned it under its common name, setwell, in The Canterbury Tales.
The name valerian may have derived from either the Latin valere (be well) or valero (strong), a reference to its odor. In fact, the only whole-hearted fans of valerian may be animals. It is reputed to have an intoxicant effect on cats at least as strong as catnip, and folk tradition reports that this was the herb that the Pied Piper used to clear the streets of Hamlin.
Regulation/Market
Valerian root extract was included as an official remedy in the U.S. Pharmacopoeia from 1820 until 1936. During World War I, it was a primary treatment for shell shock. Current surveys place valerian as the 10th most popular herb in the United States for calendar year 1998, an increase in rank from 18th the previous year.1
Pharmacology
Medicinally important constituents of valerian consist of two major and two minor classes of chemicals, although more than a hundred compounds have already been identified. The most significant compounds are found in the volatile oils, which are 0.5-1% of the dried root by weight. A variety of highly volatile monoterpenes, such as camphor, bornyl esters, and pinene, are present.
Volatile sesquiterpenes, such as valerenal and valeranone, have been identified. Much more attention has been paid to the less volatile sesquiterpenes: isovalerenic acid, valerenic acid, and acetoxyvalerenic acid. The last two compounds are found primarily in the European variant of valerian in the range of 0.1-0.3% and are the compounds most often used as marker compounds of the pharmaceutical quality of valerian. Isovalerenic acid and camphor are responsible for valerian's characteristic odor, which only develops as the root dries.
Valepotriates, unstable fatty acid esters that are responsible for the mutagenic potential of some VRE, were previously thought to be the active ingredient. However, since they are insoluble in water and unstable in heat, moisture, and acid or alkaline solutions, it is thought that they do not exert major clinical effects.2 Both gamma-aminobutyric acid (GABA) and glutamine have been found in valerian. The amounts are not felt to be high enough to cross the blood-brain barrier; their significance is uncertain.
Mechanism of Action
The active ingredients in the aqueous extract have not been identified. Whole plant alcoholic extracts and specific fractions including sesquiterpenes and valepotriates demonstrate weak binding to benzodiazepine receptor sites. These same extracts can displace muscimol from GABA-A sites.
In vitro, valerenic acid decreases degradation of GABA. Valerian extracts in animal models increase GABA in the synaptic cleft through both increased secretion of GABA and inhibition of re-uptake. No human pharmacokinetic studies on VRE were discovered.3-7
Clinical Studies
An open, multicenter observational study with 11,168 subjects (average age of 51) recorded the effects of 450 mg of dry extract of valerian root (5-6:1) given over a 10-day period. Patient self-rating found VRE successful in decreasing sleep latency in 72% of the subjects, improving discontinuous sleep in 76%, and decreasing restlessness and tension in 72%.8
A group of 128 heterogeneous subjects (wide variation in age; with and without sleep difficulty) were tested in a double-blind, placebo-controlled trial for their response over nine non-consecutive days to either 400 mg of a dry 3:1 aqueous extract of valerian root, a commercial valerian/hops combination product, or placebo.9 Sleep latency and sleep quality were superior with VRE compared with placebo (P < 0.05).
A summary of a study of "poor sleepers" with 166 subjects by Leathwood and Chauffard found even stronger differences between VRE and placebo in young poor sleepers (P < 0.01), women (P < 0.05), and smokers (P < 0.01).10 Good sleepers showed no significant effects.
Three studies looked at the effect of VRE on sleep architecture.11-13 Each of these studies had very small numbers (n = 14, 12, 20 subjects respectively) and did not test the same dose of valerian, but several common observations are worth noting. No disturbances in REM sleep were noted. Increases in slow wave delta and theta sleep, which reflected a normalized sleep pattern in stages III and IV, were reported.
The most methodologically sound study was performed by Vorbach et al on 121 subjects with a clinical diagnosis of insomnia.14 Subjects were given 600 mg of a 70% alcohol extract (5:1) of valerian root standardized to 0.4-0.6 % valerenic acid or placebo in a double-blind fashion for 28 consecutive days. Patients were measured on two standardized sleep questionnaires (SFB), a depression/mood scale (Bf-S), and a global clinical impression (GCI) scale. Questionnaires were also collected from physicians who assessed valerian's efficacy and tolerability. At 14 days, two of the four scales for patients were significantly different, but these differences were even greater at 28 days. At the end of 28 days, all scales were significantly positive for both patients and physicians. Physicians noted significant improvements in severity of disease from day 0 to day 28 (P = 0.002). Compliance with the regimen was tested and 90% of the patients received a "good" rating.
More than 70% of patients self-rating of an open, multicenter observational study of valerian root extract found all of the following except:
a. decreased sleep latency.
b. improved discontinuous sleep.
c. decreased restlessness and tension.
d. no disturbances in REM sleep.
Formulation
Valerian species are highly variable in constituents, depending on the genetic variety, growing conditions, and season of harvest. The species most often used medicinally is the European variant, Valeriana officinalis L.; preparations from different valerian species are not equivalent and should not be substituted for one another. The whole plant should not be used.
Most commercially available forms of valerian (tincture, dry root, extract, or tea) would likely be acceptable for mild, episodic insomnia. Many combination valerian products, which may contain such ingredients as hops, lemon balm, passion flower, or kava, are available. (See Table 1 for price, formulation, and dosage comparison.)
| Table 1-Sample valerian/valerian combination products | |||
| Brand | Formulation | Manufacturer's Recommended Dose | Price/Count |
| Nutritional Dynamics | 300 mg valerian root (hypo-allergenic), standardized to 1% valerenic acid per capsule | 1 capsule daily | $16.40/60 capsules |
| Rainbow Light | Valerian-kava kava super complex. Each caplet provides: 300 mg valerian rhizome and root; 34 mg kava kava root; 34 mg California poppy whole plant; 30 mg hops strobiles; 30 mg fu ling sclerotium; 16 mg polygala root; 4 mg valerian rhizome and root; 2 mg orange peel | 1-2 caplets 2-3 times daily | $14.95/60 caplets |
| Nature's Herbs | Certified potency valerian root extract concentrate (standardized for a minimum of preferred 0.8% valerenic acid) per capsule, in a synergistic base of wild countryside valerian root | 1-2 capsules bid or 3-4 capsules 30 min before bedtime | $14.89/60 capsules |
| Enzymatic Therapy Inc. | 150 mg valerian (Valeriana officinalis) extract standardized to contain 0.2-0.8% valerian acids per capsule | 1-2 capsules 30 min before bedtime, 1 capsule tid in addition to everyday diet | $13.95/90 capsules |
| Nature's Way | East Indian valerian root extracted in pure grain alcohol. Guaranteed potency: 0.015% valerenic acid (0.15 mg valerenic acid/1 ml liquid extract) | 0.5-1 ml tid | $12.95/2 oz |
| The Vitamin Shoppe | 90 mg Valeriana officinalis root (standardized to 0.8% valerenic acid) and 360 mg Valeriana officinalis root per capsule | 1-3 capsules daily | $10.75/100 capsules |
| Solaray | Valeriana officinalis root full strength tincture, grown by Trout Lake Farm, organic USP alcohol 55% | 10-20 drops at bedtime | $9.95/1.7 oz |
| Nature's Answer | Fresh valerian root in vegetable glycerine base, 0% alcohol per capsule | 5-10 drops 3-4 times daily | $9.89/1 oz |
| The Vitamin Shoppe | 450 mg 100% pure valerian root (Valeriana officinalis) | 1-2 capsules daily (capsules may be opened and prepared as tea, or dispersed in any liquid) | $6.95/100 capsules |
| Source: Online mail-order firms | |||
Dosage
The dose for dried valerian root is 2-3 g/d. In the case of chronic difficulty with sleep, 600 mg of a dry aqueous/alcoholic extract standardized from 0.4-0.8% valerenic acid, taken 1-2 hours before sleep is used over one month's time. Patients should not expect immediate relief as may be provided by a typical sleeping pill.
Toxicity/Safety
The Botanical Safety Handbook rates valerian as class 1 (herbs that can be safely consumed when used appropriately). The FDA rates valerian as GRAS (generally recognized as safe). There has been some concern about the potential toxicity of valepotriates and their degradation products, and many commercial products exclude them.15-17 Schulz advises avoidance of Mexican and Indian valerian preparations because of their high valepotriate content.4
Adverse Effects
Clinical studies show very few adverse reactions with VRE. A side effect rate of 3.3% was reported in one study and consisted of mild morning sedation and headache.3 An occasional paradoxical stimulatory effect can be seen. A single case report of serious hepatotoxicity of an over-the-counter sleep remedy containing valerian was found.18
A case report of an overdose of 20 times the therapeutic dose of valerian root (18-24 g) was reported in the literature.19 The patient presented with non-specific complaints and returned to normal without sequelae within 24 hours.
Combination valerian/hops formulations have been reported to cause morning hangovers.9
Drug/Substance Interaction
Valerian may potentiate other sedatives. Although valerian does not potentiate the effects of alcohol, it should not be combined with alcohol. It is not advised that patients drive vehicles or operate machinery for several hours after taking valerian.20
Clinical Summary
Valerian root is a mild and effective sedative and hypnotic. It is appropriate as an episodic sleep aid when taken over several weeks, but its greatest utility may be in the treatment of chronic insomnia. Its lack of serious side effects and the indication that it may normalize sleep architecture recommend consideration of this remedy.
Recommendation
To maximize the effect in chronic cases, treatment with a standardized extract for at least two weeks and preferably four weeks is recommended. There is no known toxicity associated with chronic use.
(Dr. Hardy is Medical Director of Cedars-Sinai Integrative Medicine Medical Group and Associate Clinical Professor of Medicine at the University of Southern California in Los Angeles.)
References
1. Brevcort P. The booming US botanical market: A new overview. HerbalGram 1998;44:33-48.
2. Anonymous. Valerianae radix: Valerian Root. In: European Scientific Cooperative on hytotherapy. Monographs on the Medicinal Uses of Plant Drugs. Exeter, UK: University of Exeter Press; 1997:1-10.
3. Reichert R. Valerian clinical monograph. Quart Rev Nat Med 1998; 207-215.
4. Schulz V, et al, eds. Rational Phytotherapy. Berlin: Springer-Verlag; 1998.
5. Houghton PJ. The biological activity of valerian and related plants. J Ethnopharmacol 1998;22:121-142.
6. Hendriks H, et al. Pharmacological screening of valerenal and some other components of essential oil of Valeriana officinalis. Planta Med 1981;42:62-68.
7. Rosecrans J, et al. Pharmacological investigation of certain Valeriana officinalis L. extracts. J Pharm Sci 1961;50:240-244.
8. Schmidt-Voigt J. Die behandlung nervoser schlafstorungen und innerer unruhe mit einmen rein pflanzlichen sedstivum. Therapiewoche 1986;36:663-667.
9. Leathwood PD, et al. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacol Biochem Behav 1982;17:65-71.
10. Leathwood PD, Chauffard F. Quantifying the effects of mild sedatives. J Psychiat Res 1982-83;17:115-122.
11. Schulz H, et al. The effect of valerian extract on sleep polygraphy in poor sleepers: A pilot study. Pharmaco-psychiatry 1994;27:147-151.
12. Schulz H, Jobert M. Die darstellung sdeierender/tranquilisierender wirkungen von phytopharmaka im quantifizierten EEG. Z Phytotherapie Abstractband 1995;6:10.
13. Dressing H, et al. Are valerian/melissa combinations of equal value to benzodiazepines? Therapiewoche 1992;42:726-736.
14. Vorbach E, et al. Therapie von insomnien: Wirksamkeit und verträglichkeit eines baldrianpräparats. Psychopharmakotherapie 1996;13:109-115.
15. Bos R, et al. Valeriana species. In: deSmet P, et al, eds. Adverse Effects of Herbal Drugs. 3rd ed. Berlin: Springer-Verlag; 1997:165-180.
16. Bos R, et al. Cytotoxic potential of valerian constituents and valerian tinctures. Phytomedicine 1998;5:219-225.
17. Brown D. Safety of valepotriates examined. Quart Rev Nat Med 1994; 311-312.
18. Chan TY, et al. Poisoning due to an over-the-counter hypnotic, Sleep-Qik (hyoscine, cyproheptadine, valerian). Postgrad Med J 1995;71:227-228.
19. Willey LB, et al. Valerian overdose: A case report. Vet Hum Toxicol 1995;37:364-365.
20. Albrecht M, et al. Psychopharmaceuticals and safety in traffic. Zeitschr Allegmeinmed 1995;71:1215-1221.
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