L-Tryptophan

NOTICE: This health information was not created by the University of Michigan Health System (UMHS) and may not necessarily reflect specific UMHS practices. For medical advice relating to your personal condition, please consult your doctor. Complete disclaimer

L-Tryptophan

Uses

L-Tryptophan
L-Tryptophan is an essential amino acid that the body requires to synthesize proteins and specialized molecules such as the neurotransmitter serotonin. Serotonin appears to play significant roles in sleep, emotional moods, pain control, inflammation, intestinal peristalsis, and other body functions.1

What Are "Star" Ratings?

a7_3star   Reliable and relatively consistent scientific data showing a substantial health benefit.

a7_2star   Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

a7_1star   For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

This supplement has been used in connection with the following health conditions:


Used for Amount Why
Insomnia
 1 to 2 grams at bedtime 3 stars   L-tryptophan has been used successfully for people with insomnia in many studies,including double-blind trials.

3 stars  Insomnia

1 to 2 grams at bedtime

The amino acid, L-tryptophan, a serotonin precursor, taken in amounts of 1 to 4 grams at bedtime, has been used successfully for people with insomnia in many studies,2 , 3 including double-blind trials.4 , 5 , 6 , 7 Some research indicates that people with more severe forms of insomnia may need to take L-tryptophan for several nights before improvement in sleep is noticed.8 , 9 One controlled trial found that newborns receiving a bottle feeding in which 420 mg of L-tryptophan per 2.2 lbs of body weight had been added entered quiet sleep sooner and slept for a longer time.10 Some preliminary and controlled trials have not found L-tryptophan effective,11 or have found L-tryptophan effective only for people who awaken more frequently at night compared with those who awaken less frequently.12 Several studies combined L-tryptophan with a carbohydrate-containing meal to improve L-tryptophan uptake into the brain.13 , 14 A related compound that occurs naturally in the body, 5-HTP is also converted into serotonin and might, therefore, be helpful for insomnia. In a double-blind study of people without insomnia, supplementation with 5-HTP (200 mg at 9:15 p.m. and 400 mg at 11:15 p.m.) increased rapid-eye-movement (REM) sleep, presumably indicating improved sleep quality.15 In a preliminary study of people with fibromyalgia, supplementing with 100 mg of 5-HTP three times a day improved sleep quality.16 However, additional research is needed to determine whether 5-HTP is safe and effective for people with insomnia.In a preliminary study, 5-HTP was also found to be an effective treatment for "sleep terrors,"17 a common problem in children that causes sudden awakening with persistent fear or terror, screaming, sweating, confusion, and increased heart rate.

Used for Amount Why
Pain
 2 to 4 grams per day 3 stars   Double-blind research has also shown that oral L-tryptophan can increase tolerance to acute pain.

3 stars  Pain

2 to 4 grams per day

Other amino acids may be beneficial in reducing pain. Animal research has shown that the brain chemical serotonin is involved in pain perception,18 and some,19 , 20 though not all,21 preliminary human studies have reported reduced pain sensitivity when people took 2.0 to 2.75 grams per day of L-tryptophan, a precursor of serotonin. In a double-blind study, patients recovering from gallbladder surgery reported less pain when they were given L-tryptophan intravenously in the amount of 7.5 to 15 mg per 2.2 pounds body weight.22 Double-blind research has also shown that oral L-tryptophan can increase tolerance to acute pain when taken in amounts of at least 2 grams per day.23 , 24 Two double-blind trials found that 3 to 4 grams per day of L-tryptophan along with a low-protein, high-carbohydrate diet reduced pain in people with chronic pain.25 , 26 However, one controlled study did not find L-tryptophan (50 mg per 2.2 pounds of body weight per day) helpful for people with chronic pain around the temporomandibular joint.27 No research has been published investigating the pain control potential of 5-HTP (5-hydroxytryptophan), another serotonin precursor.

Used for Amount Why
Premenstrual Syndrome
 2 to 6 grams per day, during the second half of the menstrual cycle 3 stars   Some research suggests that L-tryptophan may help balance mood symptoms associated with PMS.

3 stars  Premenstrual Syndrome

2 to 6 grams per day, during the second half of the menstrual cycle

Preliminary research suggests that imbalances of the neurotransmitter serotonin or its precursor, L-tryptophan, may be associated with PMS.28 In a double-blind trial, women with PMS who took 6 grams per day of L-tryptophan during the second half of their menstrual cycle reported a one-third reduction in the severity of abnormal mood symptoms.29 This confirmed the results of an earlier preliminary trial in which 2 grams per day of L-tryptophan taken during the second half of the menstrual cycle reduced depression and other symptoms associated with PMS.30

Used for Amount Why
Depression
 3 to 6 grams per day 2 stars   Several controlled trials have found L-tryptophan as effective as antidepressant medications. Depressed people should consult a doctor before use.  

2 stars  Depression

3 to 6 grams per day

Disruptions in emotional well-being, including depression, have been linked to serotonin imbalances in the brain.31 L-Tryptophan is the precursor to serotonin, and low body levels of L-tryptophan are associated with depression symptoms.32 Furthermore, L-tryptophan supplements have been shown to increase serotonin levels.33  Many uncontrolled studies report that 3 to 6 grams per day of L-tryptophan helps improve mood in depressed people.34 , 35 Several controlled trials found that 3 to 6 grams per day of L-tryptophan were equally as effective as antidepressant medications.36 , 37 Some,38 , 39 , 40 though not all,41 , 42 double blind studies reported that similar amounts of L-tryptophan were superior to a placebo for improving depression symptoms. Trials using amounts above 6 grams per day of L-tryptophan have often found no benefit for depression, suggesting that 3 to 6 grams per day is optimum.43 5-Hydroxytryptophan (5-HTP), a breakdown product of L-tryptophan and a serotonin precursor, has also been studied as a treatment for depression. Some trials using 200 to 300 mg per day of 5-HTP with people suffering from depression have shown signs of efficacy.44 , 45 , 46 , 47 , 48 , 49 However, much of the research was either uncontrolled or used 5-HTP in combination with antidepressant drugs. Depressed people interested in considering 5-HTP should consult a doctor.


Used for Amount Why
Obsessive-Compulsive Disorder
 6 grams per day (only under a doctor's supervision) 2 stars   With a doctor's supervision, some people with OCD have experienced some symptom relief from supplementing with L-tryptophan.

2 stars  Obsessive-Compulsive Disorder

6 grams per day (only under a doctor's supervision)

Serotonin-modifying drugs are often effective for OCD, suggesting that L-tryptophan, a precursor of serotonin, might also be effective.50 One preliminary human study reported improvement in OCD symptoms when 6 grams per day of L-tryptophan was added to therapy with a serotonin-enhancing drug.51 This treatment should be undertaken only with a doctor's supervision, because taking L-tryptophan can increase the adverse effects of serotonin-enhancing drugs. Another preliminary trial gave seven OCD patients 3 to 9 grams per day of L-tryptophan, 400 mg per day of vitamin B6, and 2 grams per day of niacin, and found considerable improvement in symptoms after one month.52 Double-blind research is needed to confirm these findings.

Used for Amount Why
Schizophrenia
 1 to 8 grams per day (under a doctor's supervision) 2 stars   L-tryptophan supplementation has occasionally been helpful for specific schizophrenia symptoms, such as aggression and memory function.

2 stars  Schizophrenia

1 to 8 grams per day (under a doctor's supervision)

Metabolism of the amino acid L-tryptophan may be abnormal in schizophrenia,53 and initially low blood levels of L-tryptophan rise when symptoms of schizophrenia improve but remain low in cases of poor recovery.54 L-tryptophan supplementation has occasionally been helpful for specific symptoms associated with schizophrenia. A small double-blind trial found that 4 to 8 grams per day of L-tryptophan reduced aggressive symptoms.55 Another double-blind trial found 1 gram per day of L-tryptophan improved memory function in schizophrenics.56 Schizoaffective disorder has features of both schizophrenia and mood disorders. A preliminary study reported that 8 grams per day of L-tryptophan improved mood symptoms in a group of patients with schizoaffective disorder, and a small, double-blind trial found that adding 9 grams per day of L-tryptophan to drug therapy was more effective for stabilizing mood in schizoaffective disorder than drug therapy plus a placebo.57 In contrast, other symptoms of schizophrenia have not responded to L-tryptophan in amounts from 1 to 20 grams per day, according to double-blind studies.58 , 59 In fact, a small preliminary study reported that schizophrenic patients on a low-tryptophan diet had improved scores on certain tests of brain function and also had small improvements in psychotic symptoms.60

Used for Amount Why
Seasonal Affective Disorder
 With doctor's supervision, 2 to 4 grams per day, increasing up to 6 grams if no improvement 2 stars   Some research suggests that L-tryptophan alone or in combination with light therapy may improve SAD symptoms.

2 stars  Seasonal Affective Disorder

With doctor's supervision, 2 to 4 grams per day, increasing up to 6 grams if no improvement

Since disturbances of serotonin metabolism may be part of the cause of SAD,61 and creating a deficiency of L-tryptophan, a precursor of serotonin, worsens symptoms of SAD,62 L-tryptophan supplementation might be helpful. One case report describes a patient with SAD who improved after taking L-tryptophan daily, 1 gram with dinner and 1 gram at bedtime.63 In a small, preliminary study, people with SAD who responded poorly or not at all to bright light therapy were given 3 grams per day of L-tryptophan for two weeks, in addition to light therapy. Nine of 14 people responded well to this combination.64 Another small preliminary study found that one of five SAD patients that did not respond to light therapy did improve after L-tryptophan supplementation in the amount of 4 grams per day, increased to 6 grams per day if no improvement occurred at the lower dose.65 A small controlled trial found that a combination of 1.5 grams of L-tryptophan, 50 mg of vitamin B6, 300 mg vitamin C, and eight ounces of fruit juice, taken three times daily, was more effective for reducing symptoms of SAD than the same combination without L-tryptophan.66 5-HTP (5-hydroxytryptophan) is a substance related to L-tryptophan that also increases serotonin production and has shown antidepressant activity.67 It may also be useful in the treatment of SAD, but there is currently no research testing this possibility.

Used for Amount Why
Anxiety
 Refer to label instructions 1 star  

Research suggests a connection between anxiety and serotonin deficiency and that its precursur L-tryptophan may help reduce anxiety in people with social axiety disorder and neurosis.

1 star  Anxiety

Animal research suggests that the brain chemical serotonin is involved in the mechanisms underlying anxiety,68 and double-blind studies have reported that creating deficiencies of L-tryptophan, a precursor of serotonin, worsens symptoms in people with anxiety disorders.69 , 70 A small double-blind trial tested a food bar containing 250 mg of L-tryptophan plus carbohydrate compared with a placebo bar containing only carbohydrate in a people diagnosed with social anxiety disorder.71 The bars were consumed one hour before doing a task designed to provoke anxiety, and anxiety was measured with two tests of heart rate changes and by ratings of anxiety by the participants. Only one of the two heart rate measures showed the L-tryptophan bar was more effective, and only slightly lower anxiety was reported when L-tryptophan was consumed.72 A double blind study in China reported that 3 grams per day of L-tryptophan improved symptoms, including anxiety, in a group of people diagnosed with “neurosis.”73 More research is needed to evaluate L-tryptophan as a treatment for anxiety disorders.

Used for Amount Why
Attention Deficit–Hyperactivity Disorder
 Refer to label instructions 1 star   Imbalances in the brain chemical serotonin, or low blood levels of its precursor, L-tryptophan, have been associated with ADHD in some (though not all) studies

1 star  Attention Deficit–Hyperactivity Disorder

Imbalances in the brain chemical serotonin, or low blood levels of its precursor, L-tryptophan, have been associated with ADHD in some,74 though not all,75 studies.76 , 77 Preliminary human studies report that creating deficiencies in L-tryptophan worsens some symptoms of ADHD. A small double blind trial found that giving children with ADHD a daily supplement of 100 mg L-tryptophan per 2.2 pounds body weight per day for one week improved behavior according to parents’ ratings, but not teachers’ ratings.78 More studies are needed to better evaluate L-tryptophan as a treatment for ADHD.

Used for Amount Why
Bulimia
 Refer to label instructions 1 star   L-tryptophan may be beneficial for people with bulimia, as this amino acid synthesizes serotonin, a hormone that helps regulate food intake and appetite.

1 star  Bulimia

Serotonin, a hormone that helps regulate food intake and appetite, is synthesized in the brain from the amino acid L-tryptophan. Preliminary data suggest that some people with bulimia have low serotonin levels.79 Researchers have reported that bulimic women with experimentally induced tryptophan deficiency tend to eat more and become more irritable compared to healthy women fed the same diet,80 , 81 though not all studies have demonstrated these effects.82

Weight-loss diets result in lower L-tryptophan and serotonin levels in women,83 which could theoretically trigger bingeing and purging in susceptible people. However, the benefits of L-tryptophan supplementation are unclear. One small, double-blind trial reported significant improvement in eating behavior, feelings about eating, and mood among women with bulimia who were given 1 gram of L-tryptophan and 45 mg of vitamin B6 three times per day.84 Other double-blind studies using only L-tryptophan have failed to confirm these findings.85 , 86 L-tryptophan is available by prescription only; most drug stores do not carry it, but “compounding” pharmacies do. Most cities have at least one compounding pharmacy, which prepares customized prescription medications to meet individual patient’s needs.

Used for Amount Why
Bulimia
(Vitamin B6)
 Refer to label instructions 1 star   Vitamin B6, when taken with L-tryptophan, has been shown to improve eating behavior, feelings about eating, and mood among women with bulimia.

1 star  Bulimia

People with eating disorders who restrict their food intake are at risk for multiple nutrient deficiencies, including protein, calcium, iron, riboflavin, niacin,87 folic acid,88 vitamin A, vitamin C,89 and vitamin B6,90 and essential fatty acids.91 A general multivitamin-mineral formula can reduce the detrimental health effects of these deficiencies.

Serotonin, a hormone that helps regulate food intake and appetite, is synthesized in the brain from the amino acid L-tryptophan. Preliminary data suggest that some people with bulimia have low serotonin levels.92 Researchers have reported that bulimic women with experimentally induced tryptophan deficiency tend to eat more and become more irritable compared to healthy women fed the same diet,93 , 94 though not all studies have demonstrated these effects.95

Weight-loss diets result in lower L-tryptophan and serotonin levels in women,96 which could theoretically trigger bingeing and purging in susceptible people. However, the benefits of L-tryptophan supplementation are unclear. One small, double-blind trial reported significant improvement in eating behavior, feelings about eating, and mood among women with bulimia who were given 1 gram of L-tryptophan and 45 mg of vitamin B6 three times per day.97 Other double-blind studies using only L-tryptophan have failed to confirm these findings.98 , 99 L-tryptophan is available by prescription only; most drug stores do not carry it, but “compounding” pharmacies do. Most cities have at least one compounding pharmacy, which prepares customized prescription medications to meet individual patient’s needs.

Used for Amount Why
Hypertension
 Refer to label instructions 1 star   The brain chemical serotonin may affect blood pressure regulation, and animal research suggests its precursur L-tryptophan may help prevent and manage hypertension.

1 star  Hypertension

The brain chemical serotonin may play a role in blood pressure regulation,100 and animal research suggests L-tryptophan, a precursor of serotonin, might be helpful in the prevention and treatment of hypertension.101 , 102 , 103 Preliminary human studies suggest that 3 to 4 grams per day of L-tryptophan can lower blood pressure in people with hypertension.104 , 105 Double blind trials are needed to confirm these promising reports.

Used for Amount Why
Migraine Headache
 Refer to label instructions 1 star   Preliminary research has found abnormally low levels of serotonin in the brains of people suffering a migraine attack, which was reversed with L-tryptophan supplements.

1 star  Migraine Headache

Interest in the effects of serotonin on the mechanisms of migraine has led to therapeutic trials using serotonin precursors such as L-tryptophan and 5-hydroxytryptophan (5-HTP).106 Preliminary research has found abnormally low levels of serotonin in the brains of people suffering a migraine attack, which was reversed with L-tryptophan supplements.107 A small double-blind trial found that four of eight people had fewer and less intense migraines while receiving L-tryptophan (500 mg every six hours).108 Larger double-blind trials are needed to better evaluate L-tryptophan as a migraine prevention supplement.

In one study, 40 people with recurrent migraines received either 5-HTP (200 mg per day) or methysergide (a drug used to prevent migraines) for 40 days. Both compounds reduced the frequency of migraines by about 50%.109 Larger amounts of 5-HTP (600 mg per day) were also found to be as effective as medications for reducing migraine headache attacks in adults in two double-blind trials.110 , 111 Migraine attacks were reduced in frequency, severity, and duration in 90% of those taking 400 mg per day of 5-HTP in a double-blind placebo-controlled trial,112 though another trial found no benefit of 5-HTP.113 In another controlled study, 400 mg per day of DL-5-HTP (another form of 5-HTP, equivalent to 200 mg per day of 5-HTP per day led to reduced consumption of pain-killing drugs and pain scores after one to two months.114 Children who suffered from migraines and had problems sleeping had an improvement in both migraines and sleep disorders after taking 5-HTP in the amount of 20 mg for every 10 pounds of body weight in a controlled trial,115 though an earlier study showed 5-HTP had no better effect than placebo for children with migraines.116

Used for Amount Why
Obesity
 Refer to label instructions 1 star   Animal research and preliminary human reports suggest that serotonin precursors such as L-tryptophan might help control appetite and promote weight loss.

1 star  Obesity

Animal research and preliminary human reports suggest that serotonin precursors such as L-tryptophan or 5-HTP (5-hydroxytryptophan) might help control appetite and promote weight loss.117 , 118 In a controlled study, increasing L-tryptophan supplementation one hour before a meal from 1 gram to 2 grams to three grams resulted in progressively fewer calories and carbohydrates being consumed during the meal at the higher L-tryptophan dosages.119 While this effect might lead to weight loss over time, a small double-blind trial did not find a significant benefit from taking 1 gram of L-tryptophan before each meal as part of a six-week weight loss program.120 Weight-loss diets result in lower L-tryptophan and serotonin levels in women,121 which could theoretically trigger cravings and make dieting more difficult.122 More research is needed to determine whether L-tryptophan might improve the results of a long-term weight loss diet.


Used for Amount Why
Restless Legs Syndrome
 1 to 2 grams at bedtime 1 star  

Preliminary research has shown some benefit reducing symptoms of restless legs syndrome and the insomnia that often accompanies it.

1 star  Restless Legs Syndrome

1 to 2 grams at bedtime

Since restless legs syndrome is often accompanied by insomnia, and L-tryptophan has been helpful for promoting sleep,123 one investigator treated two patients having both restless legs syndrome and insomnia with 1 to 2 grams of L-tryptophan at bedtime.124 In both cases restless legs symptoms improved as well as insomnia. Controlled research is needed to confirm these findings.

Used for Amount Why
Tardive Dyskinesia
 Refer to label instructions 1 star   Animal research and preliminary human reports suggest that L-tryptophan may help  reduce the severity of symptoms.

1 star  Tardive Dyskinesia

Animal research and preliminary human reports suggest that L-tryptophan may be helpful for reducing the severity of tardive dyskinesia symptoms.125 , 126 , 127 Typical supplementation has begun with 2 grams per day of L-tryptophan, increasing to as much as eight grams per day, sometimes accompanied by a low-protein, high-carbohydrate diet and 25 mg/day of niacin (nicotinic acid).128

How It Works

How to Use It

The typical Western daily diet contains 0.5-2.0 grams of L-tryptophan.129 Some authorities recommend taking L-tryptophan supplements with food or beverages high in carbohydrate and away from foods high in protein in order to improve absorption and uptake into the brain.130 , 131

Where to Find It

L-Tryptophan is found in most protein-containing foods except for gelatin.

Possible Deficiencies

Disruptions in emotional well-being, including depression and anxiety, have been linked to serotonin imbalances in the brain.132 People with fibromyalgia often have low serotonin levels in their blood.133 , 134 , 135 Supplements of L-tryptophan may increase serotonin synthesis in these cases. The cause of migraine headaches is related to abnormal serotonin function in blood vessels,136 and L-tryptophan may help correct this abnormality.

Interactions

Interactions with Supplements, Foods, & Other Compounds

“Serotonin syndrome,” a serious but uncommon condition caused by excessive amounts of serotonin, has not been reported to result from supplementation with L-tryptophan, but it can be triggered by combining L-tryptophan with drugs that increase serotonin activity (such as certain antidepressants and certain drugs used to treat migraines).137 , 138 Also, it is conceivable that L-tryptophan would increase the toxicity of St. John's wort.

Interactions with Medicines

Certain medicines interact with this supplement.

May Be Beneficial: Some medicines may increase the need for this supplement.
Avoid: Some medicines interact with this supplement, so they should not be taken together.
Check: Some interactions between this supplement and certain medicines require more explanation. Click the link to see details.

Note: The following list only includes the generic or class name of a medicine. To find a specific brand name, use the Medicines Index.

May Be Beneficial: Allopurinol
May Be Beneficial: Amitriptyline
May Be Beneficial: Amoxapine
May Be Beneficial: Benztropine
May Be Beneficial: Clomipramine
May Be Beneficial: Clozapine
May Be Beneficial: Desipramine
May Be Beneficial: Diclofenac
May Be Beneficial: Doxepin
May Be Beneficial: Imipramine
May Be Beneficial: Lithium
May Be Beneficial: Nortriptyline
May Be Beneficial: Protriptyline
May Be Beneficial: Selegiline
May Be Beneficial: Trimipramine
Avoid: Citalopram
Avoid: Escitalopram
Avoid: Fluoxetine
Avoid: Fluvoxamine
Avoid: Paroxetine
Avoid: Sertraline
Avoid: Sibutramine
Avoid: Tramadol
Avoid: Venlafaxine
Avoid: Zolpidem
Check: Almotriptan
Check: Clorazepate
Check: Eletriptan
Check: Frovatriptan
Check: Naratriptan
Check: Rizatriptan
Check: Sumatriptan
Check: Zolmitriptan

Side Effects

Side Effects

According to reports from clinical trials, most people tolerate L-tryptophan supplements without side effects. Occasionally, dizziness, stomach pain, and diarrhea have been reported.139

Until 1989, L-tryptophan was a popular nutritional supplement used for a variety of conditions.140 In that year, the US Food and Drug Administration removed L-tryptophan from the over-the-counter supplement market, citing the outbreak of an unusual ailment called eosinophilia-myalgia syndrome (EMS) that was associated with its use.141 Since then, researchers have determined that the most likely cause of this syndrome was a contaminant produced by a single manufacturer during the process of L-tryptophan production that was not effectively removed.142 , 143 Contamination errors have long since been corrected, and today L-tryptophan is again available as a supplement.

Two case reports suggested that a supplement containing L-tryptophan might have caused a scleroderma-like syndrome that resembled EMS in some ways.144 , 145 However, the supplement in one case contained a very small amount of L-tryptophan, and it also contained other ingredients.146 Larger surveys of people with scleroderma have found no link with L-tryptophan supplementation,147 , 148 so it is likely that these two cases were either a coincidence or it could be a contamination issue. 

The safety of taking L-tryptophan during pregnancy and breast-feeding is unclear. In a double-blind trial, the breathing activity of fetuses was temporarily altered when pregnant women took one gram of L-tryptophan.149 The relevance of that change to fetal health needs further study. In hamsters, supplementation with L-tryptophan during pregnancy decreased the litter size and increased the mortality of the offspring.150

References

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38. Thomson J, Rankin H, Ashcroft GW, et al.The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo. Psychol Med 1982;12:741–51.

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