Valerian for insomnia: a systematic review of randomized clinical trials

Stevinson, Clare; Ernst, Edzard

doi:10.1016/s1389-9457(99)00015-5

Cited by 174 publications

(107 citation statements)

References 19 publications

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“…Valerian (Valeriana officinalis) extracts are marketed as dietary supplements in the United States and were among the top 10 bestselling herbal supplements in the United States in 2002 (Blumenthal, 2003). Although they are currently promoted as a sedative/hypnotic, clinical trials are presently inconclusive with regard to the efficacy for insomnia (Houghton, 1999;Stevinson and Ernst, 2000;Krystal and Ressler, 2001).…”

Section: Introductionmentioning

confidence: 99%

MULTIPLE NIGHT-TIME DOSES OF VALERIAN (Valeriana officinalis) HAD MINIMAL EFFECTS ON CYP3A4 ACTIVITY AND NO EFFECT ON CYP2D6 ACTIVITY IN HEALTHY VOLUNTEERS

Donovan

DeVane²,

Chavin³

et al. 2004

Drug Metab Dispos

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ABSTRACT:Valerian (Valeriana officinalis) is a popular dietary supplement. The objective of this study was to assess the influence of a valerian extract on the activity of the drug-metabolizing enzymes cytochrome P450 2D6 (CYP2D6) and 3A4. Probe drugs dextromethorphan (30 mg; CYP2D6 activity) and alprazolam (2 mg; CYP3A4 activity) were administered orally to healthy volunteers (n ‫؍‬ 12) at baseline and again after exposure to two 500-mg valerian tablets (1000 mg) nightly for 14 days. The valerian supplement contained a total valerenic acid content of 5.51 mg/tablet. Dextromethorphan to dextorphan metabolic ratios (DMRs) and alprazolam pharmacokinetics were determined at baseline and after valerian treatment. Valerian (Valeriana officinalis) extracts are marketed as dietary supplements in the United States and were among the top 10 bestselling herbal supplements in the United States in 2002 (Blumenthal, 2003). Although they are currently promoted as a sedative/hypnotic, clinical trials are presently inconclusive with regard to the efficacy for insomnia (Houghton, 1999;Stevinson and Ernst, 2000;Krystal and Ressler, 2001).Valerian supplements contain a complex mixture of chemical constituents (Shohet et al., 2001). The main constituents are valerenic acid and its derivatives contained in the volatile oil (Houghton, 1999). These main constituents are widely thought to contribute to the putative sedative effects, although clinical effects may be a result of synergistic activity from numerous constituents. The valepotriates have also been investigated for pharmacologic activity but are relatively unstable and are often not present in most commercial supplements (Bos et al., 2002). Minor constituents include various alkaloids, furanofuran lignans, and free amino acids (Houghton, 1999). Valerian is well recognized by its unpleasant odor that is attributed to isovaleric acid formation during processing and storage.The widespread use of valerian supplements suggests that use with conventional medications is inevitable, and the potential for drug interactions is undefined (Fugh-Berman and Ernst, 2001;Markowitz et al., 2003b;Huang et al., 2004). The present study was undertaken in healthy volunteers to determine whether a valerian supplement containing known quantities of valerenic acid and its derivatives could alter the activity of two major drug-metabolizing enzymes, cytochrome P450 2D6 (CYP2D6) and CYP3A4 in healthy volunteers. These two enzymes were chosen since, together, they contribute to the metabolism of a substantial number of both prescription and nonprescription medications (Wrighton and Thummel, 2000;Zanger and Eichelbaum, 2000;Burk and Wojnowski, 2004). To our knowledge, this is the first clinical study assessing whether a standardized valerian supplement may participate in drug interactions mediated by any of the P450 enzymes. Materials and MethodsSubjects. The study was approved by the Medical University of South Carolina's Office of Research Integrity, and subjects provided written informed consent before...

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Section: Introductionmentioning

confidence: 99%

MULTIPLE NIGHT-TIME DOSES OF VALERIAN (Valeriana officinalis) HAD MINIMAL EFFECTS ON CYP3A4 ACTIVITY AND NO EFFECT ON CYP2D6 ACTIVITY IN HEALTHY VOLUNTEERS

Donovan

DeVane²,

Chavin³

et al. 2004

Drug Metab Dispos

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“…The components which are purported to have the potentiality to exert remedial effects are in general divided into the following categories: sesquiterpenes (volatile oil components that account for valerian's unpleasant odour), valepotriates, and amino acids such as GABA and glutamine. The valepotriates, for example, do not extract in aqueous media but are extracted in dilute alcohol and tend to have a more prominent anxiolytic than sleepinducing effect [100]. Because they degrade quickly, dry formulations are also available.…”

Section: Valerian (V Officinalis L)mentioning

confidence: 99%

Nutritional Modulators of Sleep Disorders

Sarrafi-Zadeh¹

2012

TONUTRAJ

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Abstract:Background: Clinical evidence indicates that insufficient sleep and poor sleep quality appear to be common consequences of shift work. These rhythms appear to have independent influence on the function of the endocrine system, circadian brain function and gastrointestinal tract. Insufficient sleep and its poor quality due to shift work interfere with beta cells, leptin and ghrelin functioning, resulting in factors for the development and exacerbation of insulin resistance. Human studies found that insufficient sleep alters the levels of leptin and ghrelin, two hormones involved in the regulation of appetite and body fat. Leptin, released by fat cells, signals the brain to feel satiety. Ghrelin, produced in the stomach, signals hunger. Investigations reported that temporarily sleep-deprived individuals experienced hormonal changes along with greater cravings for sweet and fatty foods. A further reason for their cravings is related to the stress hormone cortisol, which can rise with sleep deprivation and contribute to hunger. In addition to altered hormone levels, people who stay awake longer have more opportunity to eat, and late-night eating often includes high-caloric foods. Weight gain is only one of the many side effects of insufficient sleep, but it can lead to long-term health problems, including diabetes. Although more sleep will not automatically result in weight loss, sufficient sleep and a regular sleep schedule are critical in controlling appetite and promoting a healthy eating pattern. Research on sleep and appetite reveals a consistent link between a lower amount of sleep and a higher body mass index (BMI), a ratio of weight-to-height that indicates overweight. Studies showed those who slept less than eight hours a night were more likely to be overweight. Methods: Internet search and discussion with colleagues.Results: Recent research indicates that disruption of sleep can influence food intake and food and nutrients can influence sleep. There is evidence that high protein and carbohydrates meals can influence moods, attention and concentration among normal adult subjects with respect to age, gender and meal time. Women reported greater sleepiness after two hours of carbohydrate meal as opposed to a protein meal. On the other hand men reported greater calmness after a carbohydrate as opposed to a protein meal. Age of subjects may also influence the response to meals. After a carbohydrate or protein rich breakfast, persons older than 40 years felt more tense and less calm with a protein-rich than carbohydraterich meal. In general older subjects preferred carbohydrate than protein meals. Carbohydrate meals are also reported to impair objective performance; carbohydrate rich foods either in breakfast or lunch have exhibited negative influence on neural response such as impaired objective performance and poor sustained attention. A meal consumed close to bedtime is associated with sleep disturbances. Further, solid foods as well as large meals may cause more sleepiness than liquid foods. Studies...

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“…Psychotropic medications are predominantly used to treat these pathologies (Schreiber et al, 2008). However, the search for alternative treatments, including the deliberate use of medicinal herbs, has increased substantially in recent years with the identification of natural medicines for the treatment of insomnia and anxiety (Stevinson and Ernst, 2000;Srivastava et al, 2010;Ekor, 2014;Bakhshaei, 2017). The overuse of psychotropic medications and herbal medicines have two important consequences: the first is that use of psychotropic medications such as benzodiazepines, antidepressants, barbiturates and antipsychotics to treat insomnia and sleep disorders have many side effects such as hangover and drug addiction.…”

Section: Introductionmentioning

confidence: 99%

“…The overuse of psychotropic medications and herbal medicines have two important consequences: the first is that use of psychotropic medications such as benzodiazepines, antidepressants, barbiturates and antipsychotics to treat insomnia and sleep disorders have many side effects such as hangover and drug addiction. Secondly, medicinal herbs are easily accessible, are believed to be devoid of side effects, and are therefore commonly used to resolve sleep disorders (Stevinson and Ernst, 2000;Brattström, 2007;Bakhshaei, 2017). Ang-Lee et al (2001) have suggested discontinuing herbal medicinal products prior to surgery, and these authors considered valerian in their studies, as it is one of the herbal medicines which has information available for its direct pharmacological effects, as well as pharmacodynamic and pharmacokinetic interactions.…”

Section: Introductionmentioning

confidence: 99%

Valeriana officinalis and melatonin: Evaluation of the effects in Drosophila melanogaster rapid iterative negative geotaxis (RING) test

Cheuczuk¹,

Freitas²,

Vaz³

et al. 2017

J. Med. Plants Res.

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The rapid iterative negative geotaxis (RING) assay is a commonly used behavioral test in Drosophila based on digital imaging of flies and requires minimal equipment and space. Larval mobility can be used to reliably determine the effect of drugs on locomotion in Drosophila larvae. The effects of Valeriana officinalis extract (VoE) and melatonin (ME) were tested in Drosophila melanogaster flies and larvae. In the RING assay, the locomotor activity of flies was reduced to 30.6, 72 and 70.4% when exposed to 10 mg/ml VoE, 8 mM ME, and a combination of 8 mM ME + 10 mg/ml VoE, respectively. The performance index (PI) was reduced to 68.9% (P = 0.0058), 33.3% (P = 0.0001), and 70% (P = 0.0013) when flies were exposed to 8 mM ME, 10 mg/ml VoE, and a combination of 8 mM ME + 10 mg/ml VoE, respectively. The number of body wall contractions of Drosophila larvae (nBWC) was reduced to 47.8, 37.7 and 38.5% when larvae were exposed to 8 mM ME, 10 mg/ml VoE, and a combination of 8 mM ME + 10 mg/ml VoE, respectively. The displacement velocity (V 0 ) of larvae decreased significantly to 67.6, 60.1 and 55.6% when larvae were exposed to 8 mM ME, 10 mg/ml VoE, and a combination of 10 mg/ml VoE + 8 mM ME, respectively (P < 0.05). The effects of the VoE extract were not synergistic with ME as demonstrated by the RING assay, nBWC, and V 0 . Based on these results, valerian root extracts have demonstrated sedative effects that are better than those of melatonin in fruit flies, but did not show any increase in sedative effect when combined with melatonin.

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Valerian for insomnia: a systematic review of randomized clinical trials

Cited by 174 publications

References 19 publications

MULTIPLE NIGHT-TIME DOSES OF VALERIAN (Valeriana officinalis) HAD MINIMAL EFFECTS ON CYP3A4 ACTIVITY AND NO EFFECT ON CYP2D6 ACTIVITY IN HEALTHY VOLUNTEERS

MULTIPLE NIGHT-TIME DOSES OF VALERIAN (Valeriana officinalis) HAD MINIMAL EFFECTS ON CYP3A4 ACTIVITY AND NO EFFECT ON CYP2D6 ACTIVITY IN HEALTHY VOLUNTEERS

Nutritional Modulators of Sleep Disorders

Valeriana officinalis and melatonin: Evaluation of the effects in Drosophila melanogaster rapid iterative negative geotaxis (RING) test

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