A double-blind placebo controlled study by Levitan in 2000 found that tryptophan (2 grams per day) was used in combination with Prozac (20 grams per day) there was a significant decrease in depression scores ands an increase in sleep after four weeks of treatment (Levitan, R.D., et al. Preliminary randomized double-blind placebo controlled trial of tryptophan combined with fluoxitine to treat major depressive disorder: antidepressant and hypnotic effects. J Psychiatry Neurosci 2000 (25)

A 1987 study by Demisch, Bauer and Georgi involving 25 severe insomniacs given 2 grams of tryptophan per day over 4 weeks revealed that 76% of participants exhibited a marked improvement in sleep duration and quality at the end of the trial (Demisch K., Bauer J., and Georgi, K. Treatment of severe chronic insomnia with L-tryptophan and varying sleeping times. Pharmacopsychiatry, 1987. (20) (6); p.245-8).

Tryptophan depletion decreases serotonin levels in the brain, which in turn can lead to depression and other problems. While the study is not definitive and does not offer a solid conclusion that eating more tryptophan will enhance memory or mood, it does indicate a possible connection.

Protein source tryptophan versus pharmaceutical grade tryptophan as an efficacious treatment for chronic insomnia.

Nutr Neurosci. 2005 Apr;8(2):121-7

Hudson C, Hudson SP, Hecht T, MacKenzie J.

Biosential Inc., 1543 Bayview Avenue, Suite 346, Toronto, Ontario M4G 3B5, Canada. craighudson@biosential.com

BACKGROUND: Intact protein rich in tryptophan was not seen as an alternative to pharmaceutical grade tryptophan since protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier (BBB). Deoiled gourd seed (an extremely rich source of tryptophan-22 mg tryptophan/1 g protein) was combined with glucose, a carbohydrate that reduces serum levels of competing LNAAs which was then compared to pharmaceutical grade tryptophan with carbohydrate as well as carbohydrate alone. METHOD: Objective and subjective measures of sleep were employed to measure changes in sleep as part of a double blind placebo controlled study where subjects were randomly assigned to one of three conditions: (1) Protein source tryptophan (deoiled gourd seed) in combination with carbohydrate; (2) pharmaceutical grade tryptophan in combination with carbohydrate; (3) carbohydrate alone. SUBJECTS: Out of 57 subjects 49 of those who began the study completed the three week protocol. RESULTS: Protein source tryptophan with carbohydrate and pharmaceutical grade tryptophan, but not carbohydrate alone, resulted in significant improvement on subjective and objective measures of insomnia. Protein source tryptophan with carbohydrate alone proved effective in significantly reducing time awake during the night. CONCLUSION: Protein source tryptophan is comparable to pharmaceutical grade tryptophan for the treatment of insomnia.

PMID: 16053244 [PubMed - indexed for MEDLINE]

Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.

J Psychiatry Neurosci. 2000 Sep;25(4):337-46

Levitan RD, Shen JH, Jindal R, Driver HS, Kennedy SH, Shapiro CM.

Clarke Division, Centre for Addiction and Mental Health, Toronto, Ont. robert_levitan@camh.net

OBJECTIVE: Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Thirty individuals with major depressive disorder. INTERVENTIONS: Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo. OUTCOME MEASURES: Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures. RESULTS: During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness. CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings.

PMID: 11022398 [PubMed - indexed for MEDLINE]

5-Hydroxytryptophan: a clinically-effective serotonin precursor.

Altern Med Rev. 1998 Aug;3(4):271-80

Birdsall TC.

73541.2166@compuserve.com

5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.

PMID: 9727088 [PubMed - indexed for MEDLINE

L-tryptophan. An essential amino acid for structural and functional metabolism]

Fortschr Med. 1997 Jan 30;115(3):40-2

Loew D.

Arzt fur Pharmakologie/Klin. Pharmakologie, Universitat Frankfurt, Wuppertal.

Since the nineteen-sixties, L-Tryptophan has been used with success to treat depressive states and sleep disorders. When, in 1989, the substance was suspected of causing severe adverse reactions (EMS), approval for its use was initially suspended. It has since been shown that the undesired side effects were due not to L-Tryptophan itself, but to contaminations of the basic substance, and the suspension of approval was therefore lifted. In September 1996, L-Tryptophan was re-introduced onto the market as Ardeytropin. The present paper takes a look at the substance L-Tryptophan and discusses in particular its biochemical significance and its biokinetics/pharmacokinetics. The pharmacological basis for the use of L-Tryptophan to treat sleep disorders and depression is examined.

PMID: 9102388 [PubMed - indexed for MEDLINE]

Treatment of severe chronic insomnia with L-tryptophan and varying sleeping times.

Pharmacopsychiatry. 1987 Nov;20(6):245-8

Demisch K, Bauer J, Georgi K.

Department of Psychiatry, Hospital of the University Frankfurt/M., FRG.

Twenty-five subjects suffering from severe chronic insomnia were treated for four weeks with 2 g of L-tryptophan in combination with a schedule of varying sleeping times which caused a sleep deficiency at the beginning of treatment. A second four-week period without L-tryptophan was used as a control. Nineteen subjects (76%) experienced a markedly improved sleeping pattern after four weeks; the sleeping behavior of ten of these subjects, however, deteriorated again after the control period. Daily self-rating protocols revealed that the subjects' sleep improved significantly between the 10th and 15th day after starting treatment. Further sleep-related items such as "activity", "mood", "nervous tension", "contentment", and "quality of the preceding day" were also evaluated. This treatment schedule can thus be recommended for the treatment of severe chronic insomnia.

PMID: 3432358 [PubMed - indexed for MEDLINE]

Treatment of severe chronic insomnia with L-tryptophan: results of a double-blind cross-over study.

Pharmacopsychiatry. 1987 Nov;20(6):242-4.

Demisch K, Bauer J, Georgi K, Demisch L.

Department of Psychiatry, Hospital of the University Frankfurt/M., FRG.

Thirty-nine subjects with chronic insomnia were treated with L-tryptophan (L-TRP) in a double-blind, cross-over study. Instead of a placebo, a very low dose of 0.04 g L-TRP was used. The subjects suffered from a sleeping disorder classified as "psychophysiological, persistent". In the subgroup taking the full L-TRP (2 g) dose first, there was a significant difference between the treatment period with the full L-TRP dose and the ineffective dose (placebo). If the placebo was given first, however, there was no significant difference between the two treatment periods. It is suggested that psychological factors are responsible for the diverging results in the two subgroups of patients. On the basis of subjective ratings, it appears that L-TRP is effective in promoting sleep in cases of chronic insomnia.

PMID: 3432357 [PubMed - indexed for MEDLINE]