5-HTP and L-tryptophan. A metabolite of the essential amino acid L-tryptophan, 5-HTP is well-absorbed when taken as an oral supplement. It easily crosses the blood-brain barrier and increases the central nervous system's synthesis of the hormone serotonin. In addition to regulating behavior and mood, serotonin helps regulate sleep.8 Therefore, researchers postulate that 5-HTP supplementation may help insomniacs. Unfortunately, data on 5-HTP and sleep regulation is almost nonexistent.9^,10

Melatonin. Melatonin is produced by the pineal gland and influences circadian rhythm,11 the naturally occurring 24-hour cycle of biological processes, such as sleep and hormone secretion, which is influenced by the alternation of night and day. Exposure to light suppresses melatonin production.

Research indicates that melatonin supplementation is safe and may benefit people who have sleep disorders related to circadian rhythm, such as the blind, the elderly12 and night-shift workers.

In a meta-analysis of melatonin supplementation in the management of secondary sleep disorders (those caused by medical, neurological or substance-misuse disorders) and sleep disorders associated with sleep restriction (e.g., jet lag and shift work), researchers reviewed articles published between 1999 and 2003. The studies examined sleep-onset latency (the amount of time between lying down and falling asleep), sleep efficiency (amount of time spent asleep as a percentage of total time spent in bed), perceived sleep quality, wakefulness after sleep onset (amount of time spent awake in bed after falling sleep), total sleep time, and percentage of time in rapid-eye-movement sleep.

Six heterogeneous, randomized, controlled trials found no significant effect from 0.5 mg to 7.5 mg of melatonin on sleep-onset latency in people with secondary sleep disorders.

In individuals with sleep disorders associated with sleep restriction, nine randomized, controlled trials found no significant difference between melatonin (0.5 mg to 20 mg) and placebo for sleep latency. Five trials examining sleep efficiency also found no difference between melatonin and placebo.

The results of these reviewed studies do not support the use of melatonin as a sleep aid; however, the majority of the studies were of good methodological quality (median quality index 21 out of 29; range was 20 to 22) and revealed that melatonin is safe. Adverse side effects included headache, dizziness, nausea and drowsiness. However, the same side effects were reported with placebo.13

Though many studies indicate melatonin does not improve sleep, this supplement could help people with disrupted circadian rhythm. In a double-blind, placebo-controlled, parallel-group, 27-day study, 36 subjects ages 18 to 30 took 0.3 mg melatonin, 5.0 mg of melatonin or placebo 30 minutes before forced 6.67-hour sleep episodes. Both doses of melatonin improved sleep efficiency but did not significantly affect sleep initiation.14

Additional studies support melatonin's use in circadian rhythm disruption. In a randomized, crossover design, 17 people working two weeks on a 12-hour shift, with the first week on night shift and the second week on day shift, were given either 3 mg of melatonin or placebo one hour before bedtime, or exposed to bright light for 30 minutes during their work day to increase wakefulness, during the first four days of the night shift and the day shift. Melatonin had the greatest effect, followed by bright light. While the melatonin did not improve wakefulness during the night shift, subjects reported melatonin reduced sleepiness at work during the day shift and increased sleep by 15 to 20 minutes per day. The effects of the bright light were not statistically significant. However, when the same subjects were tested objectively on the Karolinska Sleepiness Scale and a serial reaction-time test, no significant effects were observed from the melatonin.15

Still, the Food and Drug Administration has granted orphan-drug designation (a special status conferred on drugs to treat a rare disease or condition, which qualifies the sponsor to receive tax credits and marketing incentives) to melatonin for use in treating disorders in blind individuals16 whose sleep/wake cycles often are not synchronized with day and night.17

Valerian. One of the most common herbal extracts used to mitigate insomnia is valerian root (Valeriana officinalis);¹⁸ it helps improve a person's readiness to fall asleep.19 Valerian may also alleviate symptoms of benzodiazepine withdrawal.20 Benzodiazepene is the active ingredient in many anti-anxiety and sleep-promotion medications such as Xanax, Valium and Ativan.

In a systematic review of randomized, placebo-controlled trials examining the use of valerian for improving sleep quality, researchers identified 16 total studies. However, eight of the studies had fewer than 25 patients, and many of the trials had significant methodological flaws. Among the remaining studies, preparations, outcome measures, length of treatment and herb doses (which ranged from 225 mg to 1,215 mg per day), varied considerably, making it difficult to draw a sound conclusion from this research. In addition, only two of the 16 studies used valerian extract standardized for a specific percentage of valerenic acids (the proposed biologically active components).21

Among these reviewed trials, five of seven studies that used a visual analog scale to measure sleep quality reported no statistically significant improvement in the valerian group versus the placebo group. Doses of valerian in these studies ranged from 360 mg to 600 mg every night.

Six of the 16 trials reviewed simply measured whether sleep quality was or was not improved. In these studies, valerian almost doubled the chance of sleeping better. However, further examination of these results revealed a relationship between study size and treatment effect. Participants in large studies had almost twice the likelihood of sleeping better when given valerian than those in smaller studies. This suggests the potential for publication bias, which occurs when negative studies—in this case, the smaller studies—are less likely to be published.21

Five of the studies on valerian reported no adverse events, and eight studies reported side effects in both groups (treatment and placebo) with no statistically significant difference in the frequency of adverse events between groups. Additionally, eight of the trials measured the so-called hangover effect, or the feeling of sleepiness upon waking after taking a sleep aid. Six studies showed no difference between valerian and placebo.

Another systemic review of valerian as a sleep aid examined 37 studies: 29 controlled and eight open-label trials. The most methodologically rigorous of these showed no significant differences between valerian and placebo.22 Though these studies show that valerian alone may not enhance sleep, experts point out that botanicals are complex mixtures, and their source constituents can affect study results by introducing natural variation into the treatment.

Hops. Hops are thought to affect the sleep-wake cycle,19 and are typically combined with valerian; this combination has been examined for its effect on insomnia.

A randomized four-week study examined a fixed extract of valerian and hops (500 mg of valerian and 120 mg of hops), valerian alone (500 mg) and placebo in 30 people with a sleep latency of at least 30 minutes. Valerian alone showed no effect, but the valerian/hops combination reduced sleep latency.23

In a multicenter, randomized, placebo-controlled, parallel-group study, a valerian-hops combination and diphenhydramine were studied for their potential to treat mild insomnia. People received either two nightly tablets of standardized valerian (187 mg of native extracts) and hops (41.9 mg of native extracts) for 28 days, placebo for 28 days or diphenhydramine (25 mg) for 14 days followed by placebo for 14 days. Sleep was measured by daily diaries, polysomnography, clinical outcome ratings from patients and physicians, and quality-of-life measures. The valerian-hops combination produced slightly greater, though clinically non-significant, reductions of sleep latency relative to placebo and diphenhydramine (commonly sold as Benadryl) at the end of 14 days of treatment, and greater reductions than placebo at the end of 28 days of treatment. Patients in the valerian-hops and diphenhydramine groups rated their insomnia severity lower relative to placebo at the end of 14 days of treatment. Quality of life was also significantly improved in the valerian-hops group, relative to the placebo group, at the end of 28 days.5

No serious adverse events were noted for either the valerian-hops combination or diphenhydramine, and no rebound insomnia was noted following their discontinuation. This study indicates that a valerian-hops combination and diphenhydramine appear safe, at least for short-term use, and may benefit people with mild insomnia.24

Lemon balm. The herb lemon balm has long been used as a mild sedative and sleep aid, but evidence to support its independent use is lacking.25 In one open, multicenter trial, 918 children under 12 years of age were given Euvegal forte, which is 160 mg of valerian-root dry extract, and 80 mg of lemon-balm-leaf dry extract (Melissa officinalis), for a mean duration of 31.9 days. Symptoms of insomnia were recorded before and after treatment. Before treatment, 566 patients (61.7 percent) reported daily symptoms, and 99.3 percent of patients had symptoms at least once a week. After treatment, 115 patients (12.5 percent) reported that they suffered from dyssomnia (difficulty getting to sleep or staying asleep) or restlessness every day and 71.5 percent reported they felt symptoms weekly. The combination-herb treatment improved restlessness and dyssomnia significantly during the study.26