Natural Supplements
Integrative Medical Approach to Insomnia

Thomas M. Bozzuto, D.O., Medical Director, Mind/Body Institute

While prescription sedative hypnotics are often used as a first line of therapy for insomnia, attempts to improve sleep should begin with elimination of somatic and psychiatric symptoms and modification of lifestyle factors that may affect sleep (sleep hygiene).⁵

Sleep hygiene is a technique used to help patients with insomnia identify lifestyle and environmental factors that may make it difficult to achieve or maintain sleep, such as:

• avoid stimulants such as caffeine and nicotine 12 hours before bedtime
• do not use alcohol as a sleep aid and avoid alcohol before bedtime (alcohol may promote sleep onset but decreases sleep quality)
• exercise regularly 5-6 hours before bedtime, but no closer than 3 hours
• minimize light, noise, and extreme temperatures during sleep
• eat a light snack before bed if hungry
• do not watch the clock
• do something relaxing before bedtime
• use the bed only for sleep or sex; do not read, do work, watch TV in bed
• avoid daytime napping
• get out of bed and go into another room when unable
• to fall asleep or return to sleep within 15-20 minutes. Return to bed only when sleepy again

Mind/Body Therapies involve non-pharmacologic means to change maladaptive sleep habits, reduce autonomic arousal, and alter dysfunctional beliefs that may exacerbate insomnia. These treatments produce reliable and durable benefits for many patients and avoid the untoward iatrogenic effects of many pharmacological treatments, such as tolerance, rebound insomnia and residual sedation.^6,7 These techniques include: progressive muscle relaxation where patients are instructed to tense and relax different muscle groups throughout the body to reduce the high somatic arousal often seen among patients with insomnia; biofeedback, providing visual or auditory feedback to patients to help them control certain physiologic factors such as muscle tension, to reduce somatic arousal; imagery training used to focus on pleasant or neutral thoughts in order to diminish cognitive arousal; cognitive therapy seeking to identify and modify dysfunctional beliefs about sleep by replacing them with more adaptive cognitions (patients with insomnia often exhibit unrealistic sleep expectations, performance anxiety, and amplifications of the consequences of a poor night's sleep); and multicomponent cognitive behavioral therapy which attempts to change the patient's beliefs and attitudes about insomnia and modify maladaptive behaviors that may maintain insomnia.

Alternative Remedies (Nutritional, Herbal and Homeopathic): Epidemiologic data indicate that the rate of non-prescription medications use is high among insomniacs; 40% utilize either OTC's or alcohol for their insomnia.⁸ A detailed discussion of the pharmacology of natural remedies is beyond the scope of this article, however, studies supporting the use, and mechanisms of actions of these natural substances are cited.

L-tryptophan and 5-hydroxytryptophan (5-HTP): Serotonin is an important initiator of sleep. The synthesis of CNS serotonin is dependent on tryptophan availability. Both L-tryptophan and 5-HTP have been shown to be effective in the treatment of insomnia. Current knowledge on sleep inducing effects are consistent with its effectiveness being somewhat limited to sleep-onset insomnia.^9,10 5-HTP is not dependent on a transport system for entry into the brain and clinical studies have shown 5-HTP to be dramatically superior than L-tryptophan in promoting and maintaining sleep.^11-12 One of the key benefits with 5-HTP in the treatment of insomnia is to increase sleep quality. This effect is evident by its ability to increase REM sleep (typically by 25%) while simultaneously increasing deep sleep stages 3 and 4 without increasing total sleep time.^12,13 The dose of 5-HTP for insomnia is100-300 mg taken 30-45 minutes before bedtime. Start with the lower dose for at least 3 days before increasing dosage. The dose of L-tryptophan is 3-5 grams. It should not be used with other medications (benzodiazepines, barbiturates, alcohol), supplements (melatonin), or herbs (calendula, chamomile, goldenseal, hops, Jamaican dogwood, kava, St. John's Wort, and withania) that have sedative properties.

Co-factors for serotonin synthesis: The important co-factors vitamin B₆, niacin, and magnesium should be administered with L-tryptophan or 5-HTP to insure its conversion to serotonin. Since other amino acids compete with tryptophan for transport across the blood-brain barrier, protein consumption should be avoided near administration and a carbohydrate source such as fruit or fruit juice should accompany tryptophan administration. In patients who experience flushing or hot flashes with niacin, inositol hexaniacinate should be substituted.

Valerian (Valeriana officinalis) is a perennial plant native to North America. The active ingredients (valepotriates and valerenic acid) are capable of binding to GABA receptors in a similar fashion to benzodiazepines. In subjects without insomnia, subjective sleep ratings for sleep quality and sleep latency were improved without 'hangover' the next morning.¹⁴ In a double blind study with insomniacs, subjects received a combination of valerian root (160 mg), and Melissa officinalis [lemon balm] (80 mg), a benzodiazepine (triazolam 0.125 mg), or placebo.¹⁵ In the insomniac group, the valerian preparation showed an effect comparable to the benzodiazepine as well as an increase in sleep stages 3 and 4. It did not, however, cause daytime sedation and there was no evidence of diminished concentration based on the Concentration Performance Test or impairment of physical performance. The usual dose of valerian root (standardized to 1.0-1.5% valtrate or 0.5% valerinic acid is 150-300 mg at bedtime. Valerian is on the FDA "GRAS" (generally recognized as safe) list, but may cause headache, or paradoxical excitability. It, like L-tryptophan or 5-HTP should not be taken with other sedative herbs, nutrients, or medications.

Kava (Piper mythisticum) is a member of the pepper family. Detailed analysis of active ingredients suggests that the pharmacologic activity is due to the presence of kavalactones found in the fat soluble resin of the root. The kavalactones, unlike valerian, do not bind to GABA receptors. They are thought to modify receptor domains rather than interacting with binding sites. It appears that kava acts primarily on the limbic system. It is thought that kava may promote sleep by altering the way in which the limbic system modulates emotional processes.^{16, 17} The sedative dose is 180-210 mg at bedtime. Use can cause GI irritation, headache, enlarged pupils, disturbances of oculomotor equilibrium, and allergic skin reactions. Caution with use of other sedative-hypnotic preparations.
 

Melatonin: Melatonin sales in the United States exceeds $200 million annually. Melatonin is synthesized in the pineal gland. It is produced from tryptophan, which is converted to 5-HTP, then to serotonin, N-acetylserotonin, and finally melatonin (See Table 1).18 Melatonin secretion is largely related to the night, since this is when activity of the enzyme serotonin-N-asteyltransferase is increased.19 Several double-blind trials have shown melatonin supplementation to be very effective in promoting sleep.20-24 It will only produce its effects when melatonin levels are low.

However, patients with primary insomnia were found to have significantly lower serum melatonin concentrations than normal subjects.²⁵ Some patients with depression also have a lower than expected rise in serum melatonin at night.²⁶ When melatonin is taken in low doses (0.2 to 1.0 mg) its peak serum concentrations more nearly mimic endogenous peak nocturnal values and it has few side effects. It should be taken 1 to 1½ hours before bedtime in order to allow absorption to parallel endogenous pineal melatonin release. Higher doses may actually disrupt sleep, and it has the potential to worsen depression. Its short-term administration in patients with mild sleep disorders may be effective and safe, but more data are needed to document both safety and efficacy and to determine the most appropriate dose(s). Use with fluoxetine (Prozac) is reported to improve sleep in some patients with major depressive disorder.²⁷ Melatonin can increase growth hormone levels, decrease luteinizing hormone levels. and may be useful in the treatment of benzodiazepine withdrawal in elderly patients with insomnia.²⁸ It may also affect immune function, so use with immunosupressive therapy is discouraged. Use with other herbs, medications, or nutrients with sedative properties should be avoided.

References

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25. Attenburrow ME, Dowling BA, Sharpley AL, et al.Case-control study of evening melatonin concentration in primary insomnia. BMJ 1996;312:1263.
26. Claustrat B, Chazot G, Brun J, et al. A chronobiological study of melatonon and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression. Biol Psychiat 1984:19:1215.
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Jacksonville Medicine / March, 2001

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