Supplements for Sleeplessness
Supplements for Sleeplessness
By Dónal P. O'Mathùna, PhD, Senior Lecturer in Ethics, Decision-Making & Evidence, School of Nursing & Human Sciences, Dublin City University, Ireland. Dr. O'Mathùna reports no financial relationships to this field of study.
Insomnia is relatively common and experienced around the world. Estimates have identified prevalence rates ranging from 5-50%.1 This variation is likely due to cultural differences and varying methodologies used in surveys. Incidences ranging from 20-38% are most commonly reported.2 A recent survey of U.S. workers found that 23.2% of employees experienced insomnia, contributing to 11 days of lost work annually per person impacted, at an extrapolated cost of $63 billion.3 Another well-designed survey found that 29.9% of Canadian adults experienced insomnia regularly, with 9.5% meeting the criteria for insomnia syndrome.1 This survey found that 13% of all respondents consulted a health care professional about insomnia, primarily family physicians.
Interest in complementary and alternative therapies for sleep disorders has been growing over the past two decades.4 The Canadian survey found that 9% of the sample used natural remedies for their insomnia, with more than half of the people taking these remedies at least 3 nights a week.1 However, the amount and quality of the research evidence available to guide users of herbs and supplements for insomnia remains low.4 Given the relatively high prevalence of insomnia, and the regular use of natural remedies for self-treatment, health care professionals should be aware of the most commonly used "natural" sleep remedies and the evidence for their effectiveness and side effects.
By far the most-researched herb for insomnia is valerian. Remedies made from Valeriana officinalis have been used for sleeping difficulties since ancient Greek and Roman times.5 Numerous controlled trials of valerian have been conducted and these have been systematically reviewed in recent years. The latest meta-analysis of valerian vs placebo for insomnia identified 18 randomized controlled trials (RCTs).6 Studies involving valerian in combination with other herbs were excluded. The reviewers carried out three separate meta-analyses based on how outcomes were measured. In six studies, sleep quality was measured dichotomously (asking participants if sleep improved or not), and valerian was found to provide significant benefit. The relative risk (RR) was 1.37 (95% confidence interval [CI], 1.05–1.78). In other words, those taking valerian were 1.37 times more likely to have improved sleep quality compared to those taking placebo.
However, outcome measurement with insomnia is challenging, especially when considering subjective measurements tools like questionnaires. Only two of these four studies used validated methods. Quantitative outcome measures are preferred, such as visual analogue scales (VAS) of sleep quality or latency time (LT) to get to sleep. Ten studies measured outcomes using LT in minutes and meta-analysis found no significant benefit from valerian (mean difference of 0.70 min; 95% CI, -3.44–4.83). Seven studies used VAS and likewise found no significant benefit from valerian (mean difference of -0.02; 95% CI, -0.35–0.31).
These results are similar to an earlier meta-analysis that identified 16 RCTs of valerian, either with or without other herbs.7 The most commonly reported outcome measurement method was the dichotomous question asking whether sleep improved or not. This showed significant benefit for valerian (RR 1.8; 95% CI, 1.2–2.9). The reviewers did not carry out a meta-analysis with the other studies because many different outcome measures were used and little statistical data was presented. Overall, they concluded that the quality of the studies was poor, but there was some evidence that valerian may improve sleep quality.
Another systematic review identified 37 studies.8 The authors included more studies in this analysis because they did not exclude studies using valerian along with other herbs (hops, lemon balm, or passion flower) or studies that were not double-blinded (i.e., open-label trials). They did not conduct a meta-analysis because the methodology of the trials varied widely and was generally of poor quality. They noted that most studies did not find significant differences between valerian and placebo either in healthy adults or in those with sleep disturbances or insomnia.
Overall, the evidence from larger and higher quality studies does not support the use of valerian for insomnia. While some studies have found beneficial results, the quality of these studies is low. Several studies also have examined its safety and found that adverse effects are rare and mild.8 A few cases of hepatotoxicity have been reported, but it is possible that the adverse effects were due to contaminants. A review by the National Toxicology Program found that valerian could not be shown to be the cause of the liver damage.9 The most common side effects were dizziness or headache and mild gastrointestinal effects. Valerian is thought to have sedative-hypnotic effects, and therefore may have additive effects with other sleeping agents.
Chamomile is used for many purposes, including as a natural sleep aid. Many different species are called chamomile, with German, or genuine, chamomile (Matricaria recutita) most commonly used medicinally. Roman, or English, chamomile is an unrelated plant. German chamomile leaves and flowers can be brewed as a tea or placed under the pillow to aid sleep. One recent survey in Canada found that German chamomile was the most popular herbal sleeping aid.10 Prior to September 2011, the only reported study of chamomile for insomnia was published in 1973 in which 12 hospitalized heart patients were given a strong cup of chamomile tea (strength not defined).11 Ten of the patients immediately fell into a deep sleep that lasted 90 minutes. A pilot RCT was recently published involving 34 patients with primary insomnia for at least 6 months.12 Subjects were randomized to placebo or 270 mg chamomile twice daily for 28 days. No significant differences were found for sleep outcomes as reported in sleep diaries. Secondary outcomes related to daytime functioning also were measured. These favored chamomile, but were not statistically different. Adverse effects did not differ between chamomile and placebo and all were mild and transient. The cause of any sedative effects is unknown, with studies having contradictory results. While chamomile is commonly used, evidence to guide patients is minimal, but at least side effects are minimal.
Melatonin is another highly popular supplement for sleeping problems. It became something of a "wonder drug" because of its ready availability as a dietary supplement for the relief of sleep disturbances due to jet lag and shift-work.13 At the same time, extensive research was being conducted into its role as an endogenous hormone involved in sleep regulation. This led to the identification of melatonin receptors in humans involved in synchronizing circadian rhythms.14 Although much remains unknown about melatonin's mechanism of action, it is not a hypnotic like benzodiazepines and thus does not have their adverse effects.
Clinical trials of melatonin to induce sleep have had mixed results. A 2006 systematic review identified 12 RCTs of melatonin for people with sleep disorders and another 13 trials involving sleep restriction, such as occurs with jet lag.15 Most trials were very small and the reviewers concluded there was no evidence of effectiveness in either group. The evidence also showed that melatonin was safe with short-term use.
However, the design of these trials has been questioned as more has become known about how melatonin works. Healthy volunteers taking melatonin at night, when endogenous levels are already highest may not benefit as their receptors may be saturated. Thus, in another trial when melatonin was given in the afternoon, it improved total sleep time before midnight by 2 hours compared to a control group.16
One meta-analysis included only studies using objective measures of sleep quality and involving people with insomnia who were otherwise healthy.17 This found that melatonin significantly decreased sleep latency by 3.9 min (95% CI, 2.5–5.4), increased sleep efficiency by 3.1% (95% CI, 0.7–5.5), and increased sleep duration by 13.7 min (95% CI, 3.1–24.3). Doses varied widely between 0.3 and 5 mg daily. Although a subgroup analysis by age was not reported, the reviewers concluded that studies with participants older than 55 years had more beneficial outcomes. Melatonin levels naturally decrease with age.
Melatonin has a very short half-life (about 30 min), leading to research into prolonged-release (PR) formulations. These appear to show more benefit than melatonin, although a systematic review of PR formulations has not yet been published.18 The 2010 Consensus Statement of the British Association for Psychopharmacology concluded that PR melatonin improves sleeps quality in the elderly when given for 3 weeks.18 A 6-month RCT of 2 mg PR melatonin found significantly reduced sleep latency compared to placebo in subjects over 65 years with primary insomnia (19.1 vs 1.7 min; P = 0.002).19 Benefits were apparent at 3 weeks and continued for 6 months. Adverse events were similar between groups, with no serious or prolonged side effects. Most of the research on PR melatonin has been conducted on Circadin®, a registered pharmaceutical in Europe and other countries.19 In the United States, other PR products are available as dietary supplements. In addition, research is being conducted to find more effective melatonin receptor agonists such as agomelatine, tasimelteon, and ramelteon.14 These are being developed as conventional pharmaceuticals.
Lavender oil is another natural remedy traditionally used to promote sleep. The volatile oil is typically inhaled as a fine mist that is diffused throughout a room via an atomizer and has become popular within aromatherapy.2 Animal studies support the calming effects of lavender. An early report found that when four older patients on various hypnotic drugs were taken off their medications, their sleep duration decreased.20 When lavender aroma was introduced into their ward, sleep duration increased significantly (P < 0.05). A pilot study recruited 10 people with insomnia into a single-blind, crossover trial.21 Subjects were randomized to use a vaporizer with lavender oil and then sweet almond oil, or vice versa. Each oil was used for 1 week with a 1-week washout period in between. Using the Pittsburgh Sleep Quality Index (PSQI, scoring 0 to 21), the average score decreased by 2.5 when subjects inhaled lavender, and didn't change when sweet almond oil was used.
Another small trial involved 31 healthy adults aged 18 to 30 years.22 They spent 3 consecutive nights in a sleep laboratory for adaptation, intervention, and control. Subjects laid in bed holding a vial on their chest for 2 minutes every 10 minutes for a total of 30 minutes. On the second night, half the group had lavender in their vials and the other had distilled water. For the third night, they crossed over. Over the whole night, lavender significantly increased deep sleep time (P < 0.005) using polysomnography. With questionnaires, the only significant difference noted was greater vigor upon waking for the lavender group (P < 0.05). Sleepiness before bedtime was not impacted.
The most recent trial involved 67 Taiwanese women who were randomly assigned to receive either lavender aromatherapy for 20 minutes twice weekly for 12 weeks or a sleep hygiene education program as control.23 Sleep quality was measured with the Chinese PSQI. Over the 12 weeks, those receiving lavender had significantly improved CPSQI scores (P < 0.001), while the control group showed no change.
Natural remedies are increasingly popular as sleep aids. However, the evidence for many of the most popular ones remains limited. A large number of other herbs, such as hops, lemon balm, kava, and passionflower are also used, but have even less evidence to guide decision-makers.2 As noted above, the evidence available for valerian and German chamomile do not support their effectiveness for insomnia, but the herbs are safe and commonly used. The evidence for melatonin is mixed, but as understanding of its underlying mechanism grows, it would appear to be most effective in older people and in people with sleep cycle disturbances. Also, prolonged-released formulations are more beneficial, but long-term safety has yet to be established for these. As with many other drugs originally developed from natural products, it would appear that analogues of melatonin may hold the most potential for the future. Inhalation of lavender oil, while having limited evidence, does consistently produce results that support its effectiveness.
Insomnia can be caused by several health and lifestyle factors, including sleep-disordered breathing and other primary sleep disorders. Careful consideration of these is needed to identify potential contributions to insomnia, including evening food and beverage intake, bedroom TV and lighting, physical activity, etc. Various stress factors should be considered, as well as contributions from other illnesses and side effects from medications. For those with unremitting insomnia, hypnotic drugs remain the most effective intervention. However, given their side effects, especially lingering drowsiness, melatonin or lavender inhalation may warrant a trial period. Older people in particular may benefit from prolonged-release melatonin. The lack of side effects for these natural remedies is particularly attractive. Careful monitoring of sleep quality should be carried out to identify whether the supplements are effective or if conventional medications may be necessary.
Sleep-promoting herbs are thought to act along a spectrum of action, from mild to strong, and from very safe to possibly safe. Herbal experts often recommend a step-wise approach to supplement use for insomnia, based on the severity of a patient's symptoms.
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