L-Tryptophan
Uses
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
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.
3 StarsReliable and relatively consistent scientific data showing a substantial health benefit.
2 StarsContradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1 StarFor an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.
This supplement has been used in connection with the following health conditions:
| Used for | Why |
|---|---|
3 Stars Insomnia 1 to 2 grams at bedtime | L-tryptophan has been used successfully for people with insomnia in many studies,including double-blind trials. 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,including double-blind trials. 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.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. Some preliminary and controlled trials have not found L-tryptophan effective, or have found L-tryptophan effective only for people who awaken more frequently at night compared with those who awaken less frequently. Several studies combined L-tryptophan with a carbohydrate-containing meal to improve L-tryptophan uptake into the brain. 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. In a preliminary study of people with fibromyalgia, supplementing with 100 mg of 5-HTP three times a day improved sleep quality. 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," a common problem in children that causes sudden awakening with persistent fear or terror, screaming, sweating, confusion, and increased heart rate. |
3 Stars Pain 2 to 4 grams per day | Double-blind research has also shown that oral L-tryptophan can increase tolerance to acute pain. Other amino acids may be beneficial in reducing pain. Animal research has shown that the brain chemical serotonin is involved in pain perception, and some, though not all, 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. 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. 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. 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. No research has been published investigating the pain control potential of 5-HTP (5-hydroxytryptophan), another serotonin precursor. |
3 Stars Premenstrual Syndrome 2 to 6 grams per day, during the second half of the menstrual cycle | Some research suggests that L-tryptophan may help balance mood symptoms associated with PMS. Preliminary research suggests that imbalances of the neurotransmitter serotonin or its precursor, L-tryptophan, may be associated with PMS. 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. 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. |
2 Stars Bipolar Disorder Refer to label instructions | Supplementation with L-tryptophan has led to improvement in depression in many studies, though its effect on bipolar disorder needs more study. L-tryptophan is the amino acid used by the body to produce serotonin, a chemical messenger important for proper brain function. Supplementation with L-tryptophan has led to improvement in depression in many studies, but information is limited about its effect on bipolar disorder. Case reports on two bipolar patients treated with lithium or an antidepressant drug described marked improvements when they were given 12 grams daily of L-tryptophan. Two trials using 6 grams of L-tryptophan daily for acute mania in patients with bipolar disorder found little or no improvement, but another double-blind, controlled study using 9.6 grams daily reported better results. L-tryptophan is converted to 5-HTP (5-hydroxytryptophan) before it becomes serotonin in the body. In a controlled trial, 200 mg daily of supplemental 5-HTP had antidepressant effects in bipolar patients, though it was not as effective as lithium. In a double-blind trial, patients with bipolar disorder had greater improvement with a combination of 5-HTP at 300 mg daily plus an antidepressant drug than with 5-HTP alone. |
2 Stars Depression 3 to 6 grams per day | Several controlled trials have found L-tryptophan as effective as antidepressant medications. Depressed people should consult a doctor before use. Disruptions in emotional well-being, including depression, have been linked to serotonin imbalances in the brain. L-Tryptophan is the precursor to serotonin, and low body levels of L-tryptophan are associated with depression symptoms. Furthermore, L-tryptophan supplements have been shown to increase serotonin levels. Many uncontrolled studies report that 3 to 6 grams per day of L-tryptophan helps improve mood in depressed people. Several controlled trials found that 3 to 6 grams per day of L-tryptophan were equally as effective as antidepressant medications. Some, though not all, 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. 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. 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. |
2 Stars Obesity 1,000 mg three times daily before meals | Preliminary clinical trials suggest that serotonin precursors such as L-tryptophan might help control appetite and promote weight loss. Tryptophan is the amino acid precursor to serotonin, a neurotransmitter with a critical role in mood, appetite, and metabolic regulation. High serotonin levels in the brain are associated with a sense of fullness, while low levels are linked to hunger. Unfortunately, low-calorie diets trigger decreased serotonin signaling, deterioration of mood, increased hunger and cravings, and higher likelihood of weight regain. A study that included ten healthy normal-weight men found 2- and 3-gram doses of tryptophan reduced calorie intake compared to placebo when taken before a buffet-style meal, and in a controlled trial, increasing doses of L-tryptophan from 1 gram to 2 grams to three grams before meals resulted in progressively fewer calories and carbohydrates being consumed during the meal. In a crossover trial with eight participants who had chronic obesity and food cravings, taking 1 gram of L-tryptophan before each meal as part of a six-week weight loss program led to greater weight loss than placebo, but the difference was not statistically significant, partly due to the small size of the trial. |
2 Stars Obsessive-Compulsive Disorder 6 grams per day (only under a doctor's supervision) | With a doctor's supervision, some people with OCD have experienced some symptom relief from supplementing with L-tryptophan. Serotonin-modifying drugs are often effective for OCD, suggesting that L-tryptophan, a precursor of serotonin, might also be effective. 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. 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. Double-blind research is needed to confirm these findings. |
2 Stars Schizophrenia 1 to 8 grams per day (under a doctor's supervision) | L-tryptophan supplementation has occasionally been helpful for specific schizophrenia symptoms, such as aggression and memory function. Metabolism of the amino acid L-tryptophan may be abnormal in schizophrenia, and initially low blood levels of L-tryptophan rise when symptoms of schizophrenia improve but remain low in cases of poor recovery. 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. Another double-blind trial found 1 gram per day of L-tryptophan improved memory function in schizophrenics. 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. 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. 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. |
2 Stars Seasonal Affective Disorder With doctor's supervision, 2 to 4 grams per day, increasing up to 6 grams if no improvement | Some research suggests that L-tryptophan alone or in combination with light therapy may improve SAD symptoms. Since disturbances of serotonin metabolism may be part of the cause of SAD, and creating a deficiency of L-tryptophan, a precursor of serotonin, worsens symptoms of SAD, 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. 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. 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. 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. 5-HTP (5-hydroxytryptophan) is a substance related to L-tryptophan that also increases serotonin production and has shown antidepressant activity. It may also be useful in the treatment of SAD, but there is currently no research testing this possibility. |
1 Star Alcohol Withdrawal (Glutamine, L-Tyrosine, Multivitamin, Phenylalanine) Refer to label instructions | In double-blind research, alcoholics treated with L-tyrosine combined with DLPA (D,L-phenylalanine), L-glutamine, prescription L-tryptophan, plus a multivitamin had reduced withdrawal symptoms and decreased stress. Kenneth Blum and researchers at the University of Texas have examined neurotransmitter deficiencies in alcoholics. Neurotransmitters are the chemicals the body makes to allow nerve cells to pass messages (of pain, touch, thought, etc.) from cell to cell. Amino acids are the precursors of these neurotransmitters. In double-blind research, a group of alcoholics were treated with 1.5 grams of D,L-phenylalanine (DLPA), 900 mg of L-tyrosine, 300 mg of L-glutamine, and 400 mg of L-tryptophan (now available only by prescription) per day, plus a multivitamin-mineral supplement. This nutritional supplement regimen led to a significant reduction in withdrawal symptoms and decreased stress in alcoholics compared to the effects of placebo. |
1 Star Anxiety Refer to label instructions | Research suggests a connection between anxiety and serotonin deficiency and that its precursur L-tryptophan may help reduce anxiety in people with social anxiety disorder and neurosis. Animal research suggests that the brain chemical serotonin is involved in the mechanisms underlying anxiety, and double-blind studies have reported that creating deficiencies of L-tryptophan, a precursor of serotonin, worsens symptoms in people with anxiety disorders. 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. 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. 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.” More research is needed to evaluate L-tryptophan as a treatment for anxiety disorders. |
1 Star Attention Deficit–Hyperactivity Disorder Refer to label instructions | 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 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. 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. More studies are needed to better evaluate L-tryptophan as a treatment for ADHD. |
1 Star Bulimia Refer to label instructions | L-tryptophan may be beneficial for people with bulimia, as this amino acid synthesizes serotonin, a hormone that helps regulate food intake and appetite. 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. 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, though not all studies have demonstrated these effects. Weight-loss diets result in lower L-tryptophan and serotonin levels in women, 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. Other double-blind studies using only L-tryptophan have failed to confirm these findings. 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. |
1 Star Bulimia (Vitamin B6) Refer to label instructions | Vitamin B6, when taken with L-tryptophan, has been shown to improve eating behavior, feelings about eating, and mood among women with bulimia. People with eating disorders who restrict their food intake are at risk for multiple nutrient deficiencies, including protein, calcium, iron, riboflavin, niacin,folic acid,vitamin A, vitamin C, and vitamin B6, and essential fatty acids. 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. 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, though not all studies have demonstrated these effects. Weight-loss diets result in lower L-tryptophan and serotonin levels in women, 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. Other double-blind studies using only L-tryptophan have failed to confirm these findings. 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. |
1 Star Hypertension 3 to 4 grams per day | Supplementing with L-tryptophan can temporarily raise blood serotonin levels and lower blood pressure, but whether L-tryptophan can help prevent and manage hypertension in the long-term is still unknown. The brain chemical serotonin may play a role in blood pressure regulation, and animal research suggests L-tryptophan, a precursor of serotonin, might be helpful in the prevention and treatment of hypertension. A preliminary study in 14 subjects with hypertension found 3 to 4 grams per day of L-tryptophan had an immediate blood pressure-lowering effect. However, because long-term use of L-tryptophan may alter serotonin metabolism, it is unclear whether it would be effective for preventing or treating high blood pressure. Another pilot trial reported blood pressure reductions in eight of nine volunteers with mild to moderate high blood pressure treated with 4 grams of tryptophan daily and five of eight similar subjects treated with 800 mg of 5-hydroxytryptophan (a breakdown product of tryptophan and a direct precursor of serotonin) per day. |
1 Star Migraine Headache Refer to label instructions | 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. 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). 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. 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). 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%. 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. 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, though another trial found no benefit of 5-HTP. 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. 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, though an earlier study showed 5-HTP had no better effect than placebo for children with migraines. |
1 Star Restless Legs Syndrome 1 to 2 grams at bedtime | Preliminary research has shown some benefit reducing symptoms of restless legs syndrome and the insomnia that often accompanies it. Since restless legs syndrome is often accompanied by insomnia, and L-tryptophan has been helpful for promoting sleep, one investigator treated two patients having both restless legs syndrome and insomnia with 1 to 2 grams of L-tryptophan at bedtime. In both cases restless legs symptoms improved as well as insomnia. Controlled research is needed to confirm these findings. |
1 Star Smoking Cessation Refer to label instructions | In one study, tryptophan supplements along with a high-carbohydrate diet lessened withdrawal symptoms and helped people smoke fewer cigarettes. Nicotine addiction is thought to be caused by increased stimulation of nerve receptors for various brain chemicals, including serotonin. Withdrawal symptoms that accompany smoking cessation could be related to the sudden drop in nerve receptor stimulation. However, a double-blind study found that depleting blood levels of tryptophan, the precursor to serotonin, had no effect on withdrawal symptoms after five hours of smoking abstinence. In a controlled study, a daily tryptophan supplement (50 mg per 2.2 pounds of body weight) along with a high-carbohydrate diet (which increases brain uptake of tryptophan) was added to a smoking cessation program. While rates of complete abstinence were not significantly affected, tryptophan plus a high-carbohydrate diet lessened withdrawal symptoms and helped participants smoke fewer cigarettes. More research is needed to clarify whether supplementing with tryptophan or other serotonin precursors might help support smoking cessation. |
1 Star Tardive Dyskinesia Refer to label instructions | Animal research and preliminary human reports suggest that L-tryptophan may help reduce the severity of symptoms. Animal research and preliminary human reports suggest that L-tryptophan may be helpful for reducing the severity of tardive dyskinesia symptoms. 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). |
How to Use It
The typical Western daily diet contains 0.5-2.0 grams of L-tryptophan.2 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.3, 4
Where to Find It
Possible Deficiencies
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).10, 11 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.
Replenish Depleted Nutrients
- Clozapine
Some people who take clozapine become mentally depressed after taking the drug for a few weeks. Studies have shown that clozapine can reduce blood levels of the amino acid L-tryptophan, which is often deficient in people with depression. More controlled research is needed to determine whether the interaction is significant and whether individuals taking clozapine might benefit from supplemental L-tryptophan or 5-hydroxytryptophan (5-HTP).
- Diclofenac
Diclofenac causes complex changes to L-tryptophan levels in the blood, but the clinical implications of this are unknown. More research is needed to determine whether supplementation with L-tryptophan is a good idea for people taking diclofenac.
Reduce Side Effects
none
Support Medicine
- Allopurinol
In a preliminary study, seven of eight individuals with severe mental depression showed improvement when they took L-tryptophan and allopurinol; of these seven, five experienced full remission. Controlled research is necessary to determine whether this combination might be more effective for severe depression than standard treatment.
- Amitriptyline
Combination of 6 grams per day L-tryptophan and 1,500 mg per day niacinamide (a form of vitamin B3) with imipramine has shown to be more effective than imipramine alone for people with bipolar disorder. These levels did not improve the effects of imipramine in people with depression. Lower amounts (4 grams per day of L-tryptophan and 1,000 mg per day of niacinamide) did show some tendency to enhance the effect of imipramine.
The importance of the amount of L-tryptophan was confirmed in other studies, suggesting that if too much L-tryptophan (6 grams per day) is used, it is not beneficial, while levels around 4 grams per day may make tricyclic antidepressants work better.
- Amoxapine
Combination of 6 grams per day L-tryptophan and 1,500 mg per day niacinamide (a form of vitamin B3) with imipramine has shown to be more effective than imipramine alone for people with bipolar disorder. These levels did not improve the effects of imipramine in people with depression. Lower amounts (4 grams per day of L-tryptophan and 1,000 mg per day of niacinamide) did show some tendency to enhance the effect of imipramine.
The importance of the amount of L-tryptophan was confirmed in other studies, suggesting that if too much L-tryptophan (6 grams per day) is used, it is not beneficial, while levels around 4 grams per day may make tricyclic antidepressants work better.
- Benztropine
Akathisia is an adverse reaction to anti-psychotic drugs, where a person has an uncontrollable desire to be in constant motion. One preliminary report suggested that 4,000 mg of L-tryptophan and 25 mg niacin per day taken with benztropine enhances the treatment of akathisia. Controlled studies are necessary to determine whether L-tryptophan and niacin supplements might benefit most people taking benztropine who experience adverse reactions to anti-psychotic drugs.
- Clomipramine
Combination of 6 grams per day L-tryptophan and 1,500 mg per day niacinamide (a form of vitamin B3) with imipramine has shown to be more effective than imipramine alone for people with bipolar disorder. These levels did not improve the effects of imipramine in people with depression. Lower amounts (4 grams per day of L-tryptophan and 1,000 mg per day of niacinamide) did show some tendency to enhance the effect of imipramine.
The importance of the amount of L-tryptophan was confirmed in other studies, suggesting that if too much L-tryptophan (6 grams per day) is used, it is not beneficial, while levels around 4 grams per day may make tricyclic antidepressants work better.
- Desipramine
Combination of 6 grams per day L-tryptophan and 1,500 mg per day niacinamide (a form of vitamin B3) with imipramine has shown to be more effective than imipramine alone for people with bipolar disorder. These levels did not improve the effects of imipramine in people with depression. Lower amounts (4 grams per day of L-tryptophan and 1,000 mg per day of niacinamide) did show some tendency to enhance the effect of imipramine.
The importance of the amount of L-tryptophan was confirmed in other studies, suggesting that if too much L-tryptophan (6 grams per day) is used, it is not beneficial, while levels around 4 grams per day may make tricyclic antidepressants work better.
- Doxepin
Combination of 6 grams per day L-tryptophan and 1,500 mg per day niacinamide (a form of vitamin B3) with imipramine has shown to be more effective than imipramine alone for people with bipolar disorder. These levels did not improve the effects of imipramine in people with depression. Lower amounts (4 grams per day of L-tryptophan and 1,000 mg per day of niacinamide) did show some tendency to enhance the effect of imipramine.
The importance of the amount of L-tryptophan was confirmed in other studies, suggesting that if too much L-tryptophan (6 grams per day) is used, it is not beneficial, while levels around 4 grams per day may make tricyclic antidepressants work better.
- Imipramine
Combination of 6 grams per day L-tryptophan and 1,500 mg per day niacinamide (a form of vitamin B3) with imipramine has shown to be more effective than imipramine alone for people with bipolar disorder. These levels did not improve the effects of imipramine in people with depression. Lower amounts (4 grams per day of L-tryptophan and 1,000 mg per day of niacinamide) did show some tendency to enhance the effect of imipramine.
The importance of the amount of L-tryptophan was confirmed in other studies, suggesting that if too much L-tryptophan (6 grams per day) is used, it is not beneficial, while levels around 4 grams per day may make tricyclic antidepressants work better.
- Lithium
A small double-blind study found that combining 2–4 grams three times per day of L-tryptophan with lithium significantly improved symptoms in people with bipolar disorder or a mild form of schizophrenia. L-tryptophan is only available from doctors. It should be taken several hours before or after meals.
- Nortriptyline
Combination of 6 grams per day L-tryptophan and 1,500 mg per day niacinamide (a form of vitamin B3) with imipramine has shown to be more effective than imipramine alone for people with bipolar disorder. These levels did not improve the effects of imipramine in people with depression. Lower amounts (4 grams per day of L-tryptophan and 1,000 mg per day of niacinamide) did show some tendency to enhance the effect of imipramine.
The importance of the amount of L-tryptophan was confirmed in other studies, suggesting that if too much L-tryptophan (6 grams per day) is used, it is not beneficial, while levels around 4 grams per day may make tricyclic antidepressants work better.
- Protriptyline
Combination of 6 grams per day L-tryptophan and 1,500 mg per day niacinamide (a form of vitamin B3) with imipramine has shown to be more effective than imipramine alone for people with bipolar disorder. These levels did not improve the effects of imipramine in people with depression. Lower amounts (4 grams per day of L-tryptophan and 1,000 mg per day of niacinamide) did show some tendency to enhance the effect of imipramine.
The importance of the amount of L-tryptophan was confirmed in other studies, suggesting that if too much L-tryptophan (6 grams per day) is used, it is not beneficial, while levels around 4 grams per day may make tricyclic antidepressants work better.
- Selegiline
Both L-tryptophan and 5-HTP have been used to treat depression. One controlled study showed that taking selegiline at the same time as 5-HTP enhanced the antidepressant effect when compared with 5-HTP alone. Further research is needed to determine whether taking selegiline and 5-HTP together might result in unwanted side effects.
- Trimipramine
Combination of 6 grams per day L-tryptophan and 1,500 mg per day niacinamide (a form of vitamin B3) with imipramine has shown to be more effective than imipramine alone for people with bipolar disorder. These levels did not improve the effects of imipramine in people with depression. Lower amounts (4 grams per day of L-tryptophan and 1,000 mg per day of niacinamide) did show some tendency to enhance the effect of imipramine.
The importance of the amount of L-tryptophan was confirmed in other studies, suggesting that if too much L-tryptophan (6 grams per day) is used, it is not beneficial, while levels around 4 grams per day may make tricyclic antidepressants work better.
Reduces Effectiveness
none
Potential Negative Interaction
- Almotriptan
Triptans work by stimulating serotonin receptors in the brain. 5-HTP (5-Hydroxytryptophan) and L-tryptophan are converted to serotonin in the brain, and taking them with eletriptan could increase eletriptan-induced side effects. However, no interactions have yet been reported with eletriptan and 5-HTP or L-tryptophan.
- Citalopram
Citalopram increases serotonin activity in the brain. 5-HTP and L-tryptophan are converted to serotonin in the brain, and taking either of these compounds with citalopram may increase citalopram-induced side effects. Dietary supplements of L-tryptophan (available only by prescription from special compounding pharmacists) taken with paroxetine (a drug that has similar actions as citalopram) caused headache, sweating, dizziness, agitation, restlessness, nausea, vomiting, and other symptoms.
Some doctors have used small amounts of L-tryptophan in combination with SSRIs, to increase their effectiveness. However, because of the potential for side effects, 5-HTP and L-tryptophan should never be taken in combination with citalopram or other SSRIs, unless a doctor is closely monitoring the combination. Foods rich in L-tryptophan do not appear to interact with citalopram or other SSRIs.
- Eletriptan
Eletriptan works by stimulating serotonin receptors in the brain. 5-HTP (5-Hydroxytryptophan) and L-tryptophan are converted to serotonin in the brain, and taking them with eletriptan could increase eletriptan-induced side effects. However, no interactions have yet been reported with eletriptan and 5-HTP or L-tryptophan.
- Escitalopram
Escitalopram increases serotonin activity in the brain. 5-HTP and L-tryptophan are converted to serotonin in the brain, and taking either of these compounds with escitalopram may increase escitalopram-induced side effects. Dietary supplements of L-tryptophan (available only by prescription from special compounding pharmacists) taken with paroxetine (a drug that has similar actions as escitalopram) caused headache, sweating, dizziness, agitation, restlessness, nausea, vomiting, and other symptoms.
Some doctors have used small amounts of L-tryptophan in combination with SSRIs, to increase their effectiveness. However, because of the potential for side effects, 5-HTP and L-tryptophan should never be taken in combination with escitalopram or other SSRIs, unless a doctor is closely monitoring the combination. Foods rich in L-tryptophan do not appear to interact with escitalopram or other SSRIs.
- Fluoxetine
L-tryptophan is an amino acid found in protein-rich foods. Foods rich in L-tryptophan are not believed to cause any problems during fluoxetine use. However, dietary supplements of L-tryptophan taken during fluoxetine treatment have been reported to cause headache, sweating, dizziness, agitation, restlessness, nausea, vomiting, and other symptoms.
- Fluvoxamine
Fluvoxamine works by increasing serotonin activity in the brain. 5-HTP (5-Hydroxytryptophan) and L-tryptophan are converted to serotonin in the brain, and taking them with fluvoxamine may increase fluvoxamine-induced side effects. Until more is known, 5-HTP and L-tryptophan should not be taken with any SSRI drug, including fluvoxamine.
- Frovatriptan
Triptans work by stimulating serotonin receptors in the brain. 5-HTP (5-Hydroxytryptophan) and L-tryptophan are converted to serotonin in the brain, and taking them at the same time as 5-HT1 agonists could increase unwanted side effects. However, at the time of this writing there are no known interactions with 5-HT1 agonists and 5-HTP or L-tryptophan.
- Olanzapine-Fluoxetine
Triptans work by stimulating serotonin receptors in the brain. 5-HTP (5-Hydroxytryptophan) and L-tryptophan are converted to serotonin in the brain, and taking them at the same time as 5-HT1 agonists could increase unwanted side effects. However, at the time of this writing there are no known interactions with 5-HT1 agonists and 5-HTP or L-tryptophan.
- Paroxetine
Paroxetine increases serotonin activity in the brain. 5-HTP and L-tryptophan are converted to serotonin in the brain, and taking either of these compounds with paroxetine may increase paroxetine-induced side effects. Dietary supplements of L-tryptophan (available only by prescriptions from special compounding pharmacists) taken with paroxetine caused headache, sweating, dizziness, agitation, restlessness, nausea, vomiting, and other symptoms. Some doctors have used small amounts of L-tryptophan in combination with SSRIs, to increase the effectiveness of the latter. However, because of the potential for side effects, 5-HTP and L-tryptophan should never be taken in combination with paroxetine or other SSRIs, unless the combination is being closely monitored by a doctor. Foods rich in L-tryptophan do not appear to interact with paroxtine or other SSRIs.
On the other hand, the combination of 45 mg DL-tryptophan (a synthetic variation of L-tryptophan) per pound of body weight (a relatively high dose) with zimelidine, a drug with a similar action to paroxetine, did not cause these side effects in another trial.
- Paroxetine Mesylate
Sertraline increases serotonin activity in the brain. 5-HTP and L-tryptophan are converted to serotonin in the brain, and taking either of these compounds with sertraline may increase sertraline-induced side effects.
In one report, dietary supplements of L-tryptophan (available only by prescriptions from special compounding pharmacists) taken with paroxetine (a drug similar to sertraline) caused headache, sweating, dizziness, agitation, restlessness, nausea, vomiting, and other symptoms. On the other hand, the combination of 45 mg DL-tryptophan (a synthetic variation of L-tryptophan) per pound of body weight (a relatively high dose) with zimelidine, a drug with a similar action to sertraline, did not cause these side effects in another trial. Some doctors have used small amounts of L-tryptophan in combination with SSRIs, to increase the effectiveness of the latter. However, because of the potential for side effects, 5-HTP and L-tryptophan should never be taken in combination with sertraline or other SSRIs, unless the combination is being closely monitored by a doctor. Foods rich in L-tryptophan do not appear to interact with sertraline or other SSRIs.
- Rizatriptan
Triptans work by stimulating serotonin receptors in the brain. 5-HTP (5-Hydroxytryptophan) and L-tryptophan are converted to serotonin in the brain, and taking them at the same time as 5-HT1 agonists could increase unwanted side effects. However, at the time of this writing there are no known interactions with 5-HT1 agonists and 5-HTP or L-tryptophan.
- Sertraline
Sertraline increases serotonin activity in the brain. 5-HTP and L-tryptophan are converted to serotonin in the brain, and taking either of these compounds with sertraline may increase sertraline-induced side effects.
In one report, dietary supplements of L-tryptophan (available only by prescriptions from special compounding pharmacists) taken with paroxetine (a drug similar to sertraline) caused headache, sweating, dizziness, agitation, restlessness, nausea, vomiting, and other symptoms. On the other hand, the combination of 45 mg DL-tryptophan (a synthetic variation of L-tryptophan) per pound of body weight (a relatively high dose) with zimelidine, a drug with a similar action to sertraline, did not cause these side effects in another trial. Some doctors have used small amounts of L-tryptophan in combination with SSRIs, to increase the effectiveness of the latter. However, because of the potential for side effects, 5-HTP and L-tryptophan should never be taken in combination with sertraline or other SSRIs, unless the combination is being closely monitored by a doctor. Foods rich in L-tryptophan do not appear to interact with sertraline or other SSRIs.
- Sibutramine
The amino acids L-tryptophan and 5-hydroxytryptophan (5-HTP) are occasionally used to treat mental depression. Taking sibutramine with L-tryptophan or 5-HTP might result in a rare, but serious group of symptoms known as “serotonin syndrome.” Symptoms associated with serotonin syndrome may include confusion, anxiety, muscle weakness, incoordination, and vomiting. Therefore, individuals taking sibutramine should avoid supplementing with L-tryptophan and 5-HTP.
- Sumatriptan
Sumatriptan works by stimulating serotonin receptors in the brain. 5-HTP (5-Hydroxytryptophan) and L-tryptophan are converted to serotonin in the brain, and taking them with sumatriptan could increase sumatriptan-induced side effects. However, no interactions have yet been reported with sumatriptan and 5-HTP or L-tryptophan.
- Sumatriptan Succinate
Sumatriptan works by stimulating serotonin receptors in the brain. 5-HTP (5-Hydroxytryptophan) and L-tryptophan are converted to serotonin in the brain, and taking them with sumatriptan could increase sumatriptan-induced side effects. However, no interactions have yet been reported with sumatriptan and 5-HTP or L-tryptophan.
- Tramadol
Tramadol, which blocks serotonin reuptake in the brain, has been associated with two cases of serotonin syndrome. 5-HTP and L-tryptophan are converted to serotonin in the brain. While no interactions have yet been reported with tramadol and 5-HTP or L-tryptophan, taking 5-HTP or L-tryptophan with tramadol may increase the risk of tramadol-induced side effects, including serotonin syndrome.
- Venlafaxine
Venlafaxine, a potent serotonin reuptake inhibitor, has been associated with several cases of serotonin syndrome. 5-HTP and L-tryptophan are converted to serotonin in the brain, and taking them with venlafaxine may increase venlafaxine-induced side effects. While no interactions with venlafaxine and 5-HTP or L-tryptophan have been reported, until more is known, people taking venlafaxine are cautioned to avoid 5-HTP or L-tryptophan.
- Zolmitriptan
Zolmitriptan works by stimulating serotonin receptors in the brain. 5-HTP (5-Hydroxytryptophan) and L-tryptophan are converted to serotonin in the brain, and taking them with zolmitriptan could increase zolmitriptan-induced side effects. However, no interactions have yet been reported with zolmitriptan and 5-HTP or L-tryptophan.
- Zolpidem
Nine cases of zolpidem-induced hallucinations associated with serotonin reuptake inhibiting antidepressants have been reported, some lasting for several hours. 5-HTP (5-Hydroxytryptophan) and L-tryptophan are converted to serotonin in the brain, and taking them with zolpidem may increase zolpidem-induced hallucinations, though no interactions have yet been reported with zolpidem and 5-HTP or L-tryptophan.
Explanation Required
- Clorazepate
Test tube studies show that L-tryptophan and clorazepate dipotassium interact in the blood in such a way that the actions of the drug may be enhanced when high amounts of L-tryptophan are ingested. Controlled research is needed to determine the significance of this interaction and to investigate possible interactions between clorazepate and 5-hydroxytryptophan, a supplement related to L-tryptophan.
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.12
Until 1989, L-tryptophan was a popular nutritional supplement used for a variety of conditions.13 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.14 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.15, 16 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.17, 18 However, the supplement in one case contained a very small amount of L-tryptophan, and it also contained other ingredients.19 Larger surveys of people with scleroderma have found no link with L-tryptophan supplementation,20, 21 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.22 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.23
1. Guyton AC, Hall JE. Textbook of Medical Physiology, 9th ed. Philadelphia: W. B. Saunders, 1996.
2. Hartmann E, Spinweber CL. Sleep induced by L-tryptophan. Effect of dosages within the normal dietary intake. J Nerv Ment Dis 1979;167:497-9.
3. Snyder S, Hams G. Serotoninergic agents in the treatment of isolated sleep paralysis. Am J Psychiatry 1982;139:1202-3.
4. Fernstrom JD, Faller DV. Neutral amino acids in the brain: Changes in response to food ingestion. J Neurochem 1978;30:1531-8.
5. Hartmann E, Spinweber CL. Sleep induced by L-tryptophan. Effect of dosages within the normal dietary intake. J Nerv Ment Dis 1979;167:497-9.
6. Snyder S, Hams G. Serotoninergic agents in the treatment of isolated sleep paralysis. Am J Psychiatry 1982;139:1202-3.
7. Fernstrom JD, Faller DV. Neutral amino acids in the brain: Changes in response to food ingestion. J Neurochem 1978;30:1531-8.
8. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev 2002; (1):CD003198.
9. Morgan B, Morgan R. Brainfood: nutrition and your brain. Tucson, Arizona: The Body Press, 1987.
10. Martin TG. Serotonin syndrome. Ann Emerg Med 1996;28:520-6.
11. Messiha FS. Fluoxetine: adverse effects and drug-drug interactions. J Toxicol Clin Toxicol 1993;31:603-30.
12. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev 2002; (1):CD003198.
13. Morgan B, Morgan R. Brainfood: nutrition and your brain. Tucson, Arizona: The Body Press, 1987.
14. Blackburn WD. Eosinophilic myalgia syndrome. Semin Arth Rheum 1997;26:788-93.
15. Slutsker L, Hoesly FC, Miller L, et al. Eosinophilia-myalgia syndrome associated with exposure to tryptophan from a single manufacturer. JAMA 1990;264:213-7.
16. Kilbourne EM, Philen RM, Kamb ML, Falk H. Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome. J Rheumatol Suppl 1996;46:81-8.
17. Schlessel K, Greenwald R, Hirschfield L. Scleroderma-like fasciitis without eosinophilia after L-tryptophan ingestion. J Rheumatol 1991;18:779-82.
18. Feroze K, Venkitakrishnan S, Manoj J. L-tryptophan and scleroderma: significance of nutritional supplements containing L-tryptophan. J Postgrad Med 2008;54:235-6.
19. Feroze K, Venkitakrishnan S, Manoj J. L-tryptophan and scleroderma: significance of nutritional supplements containing L-tryptophan. J Postgrad Med 2008;54:235-6.
20. Mensing H. L-tryptophan ingestion does not induce progressive systemic sclerosis (scleroderma). Dermatology 1992;185:173-4.
21. Freundlich B, Werth VP, Rook AH, et al. L-tryptophan ingestion associated with eosinophilic fasciitis but not progressive systemic sclerosis. Ann Intern Med 1990;112:758-62.
22. Devoe LD, Castillo RA, Searle NS, Searle JR. Maternal dietary substrates and human fetal biophysical activity. I. The effects of tryptophan and glucose on fetal breathing movements. Am J Obstet Gynecol 1986;155:135-9.
23. Meier AH, Wilson JM. Tryptophan feeding adversely influences pregnancy. Life Sci 1983;32:1193-6.
Last Review: 05-24-2015
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