Known interactions

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Information about L-tryptophan

Scientific Name: Tryptophan

Other Names: L-tryptophan

Who is this for?

While the sale of tryptophan as a dietary supplement is not prohibited in the United States, the U.S. Food and Drug Administration (FDA) has issued a statement expressing strong concerns about the safety of its use. In 1989 and 1990, deaths and serious illnesses were attributed to the use of contaminated tryptophan. At that time, the FDA instituted a recall of supplemental tryptophan. Although the contamination is thought to have been limited to products made by only one manufacturer, the exact reasons for the contamination are unclear. Tryptophan may now be purchased as a dietary supplement, again. However, the use of supplemental tryptophan is not recommended.

The body uses tryptophan to produce melatonin, a hormone that regulates sleep; niacin (vitamin B3), which is essential for normal gastrointestinal and nerve processes; and serotonin, a neurotransmitter involved in controlling moods and appetite.

Tryptophan is well-known as an antidepressant, because it converts into serotonin in the body. Serotonin is a neurotransmitter that helps to moderate depression and related disorders such as premenstrual syndrome. Neurotransmitters are chemicals that carry messages from nerve cells to other cells. Unlike antidepressant drugs known as selective serotonin reuptake inhibitors (SSRIs) that only preserve the amounts of serotonin already in circulation, tryptophan actually changes into additional serotonin. By increasing the amount of serotonin in the blood, tryptophan may also increase serotonin’s antidepressant effects. Tryptophan is also involved in the body’s regulation of sleep. It has been shown in human clinical studies that low levels of tryptophan contribute to insomnia. Increasing tryptophan may help to normalize sleep patterns. However, higher than usual levels of tryptophan in the blood have been associated with conditions such as chronic fatigue syndrome. Whether the high tryptophan levels are a cause of the condition or a result from it are unclear. More studies are underway to better understand tryptophan’s role in both depression and sleep disorders.

In other research, studies of tryptophan’s effect on eating may show that raising tryptophan levels in the body may decrease appetite – especially for carbohydrates. While the exact reasons for this effect have not been identified, it is known that consuming carbohydrates increases serotonin levels, making carbohydrates among the most often over consumed “comfort foods”. In general, eating them makes most individuals feel less depressed due to the increased serotonin levels they produce. Substituting tryptophan for carbohydrate foods may also reduce depressed feelings. For similar reasons, tryptophan may also have a role in helping smokers to quit.

When should I be careful taking it?

In 1989 and 1990, taking tryptophan was associated with a severe condition known as eosinophilia-myalgia syndrome. Although the exact causes for the outbreak are still not completely known, it is believed that a unique manufacturing process used by one company either introduced contaminants or caused reactions that formed toxic substances within the tryptophan that was produced. Eosinophilia-myalgia syndrome involves increased production of eosinophils (one type of white blood cells). It has potentially disabling symptoms that include fever, muscle pain, rash, and swelling in the arms and legs. Over 35 deaths were attributed to the toxic tryptophan and about 1500 more individuals are thought to have been permanently disabled by it.

Beginning about 1990, the sale of tryptophan as a single agent was restricted for some years in the United States. Although it continued to be included in some combination amino acid products and some special formulas, those products were used only with strict supervision from a healthcare professional. Currently, although tryptophan is back on the U.S. market as a non-prescription dietary supplement, the quality of any tryptophan product cannot be guaranteed.

While taking tryptophan is not recommended for anyone, certain individuals should be especially careful to avoid it.

  • In animal studies, high doses of tryptophan are believed to have caused birth defects. Additionally, high levels of tryptophan may cause developing babies to have serious breathing problems before they are born. Therefore, pregnant women should never take supplemental tryptophan.
  • Tryptophan is known to pass into the breast milk of new mothers, but its possible effects in infants are not known. Therefore, tryptophan should also be avoided during breast-feeding.
  • Individuals who have kidney or liver conditions should not take supplemental tryptophan due to the possibility that it may worsen these conditions.
  • Tryptophan may cause sedation, which may result in sleepiness or mental confusion during the daytime. Individuals who choose to take it should be careful when driving or performing other tasks that require alertness.

What side effects should I watch for?

In the early 1990s, the FDA withdrew tryptophan from the U.S. market due to a rare but definite association with fatal or disabling eosinophilia-myalgia syndrome. This condition may cause symptoms that include fatigue, fever, muscle and joint pain, rash, and swelling in the face, arms, or legs. Some individuals may be more likely to experience problems, but who might be affected is impossible to determine before symptoms develop. The severity of the possible results is also unpredictable.

Less Severe Side Effects

Oral tryptophan has also been associated with less serious side effects that include:

  • Blurry vision
  • Daytime drowsiness
  • Dry mouth
  • Headaches
  • Muscle incoordination
  • Nausea

What interactions should I watch for?

Prescription Drugs

When tryptophan is used with prescription drugs that promote sleepiness, the effects of the drug may be exaggerated, resulting in sedation or mental impairment. Prescription drugs that can cause sleepiness include:

  • Anticonvulsants such as carbamazepine, phenytoin and valproic acid
  • Barbiturates such as phenobarbital
  • Benzodiazepines such as alprazolam and diazepam
  • Drugs for insomnia such as Ambien and Sonata
  • Tricyclic antidepressants such as amitriptyline, amoxapine, doxepin and nortriptyline

Because it may block the effects of the enzyme monoamine oxidase, tryptophan may possibly increase the effects and the risk of side effects — including dangerous rapid increases in blood pressure — from prescription drugs that also interfere with monoamine oxidase. These drugs, known as monoamine oxidase inhibitors or MAOIs, include:

  • isocarboxazid (Marplan)
  • phenelzine (Nardil)
  • tranylcypromine (Parnate)

If tryptophan is taken with prescription antidepressants such as fluoxetine (Prozac), paroxetine (Paxil), or Zoloft that belong to the class known as selective serotonin re-uptake inhibitors (SSRIs), serotonin levels may become excessive. Serotonin syndrome, a rare but potentially dangerous condition, may develop. Uncontrolled serotonin syndrome may result in coma, seizures, and death. Symptoms of serotonin syndrome include:

  • Confusion
  • Euphoria
  • Fever
  • Hallucinations
  • Inability to coordinate muscles
  • Restlessness
  • Shakiness
  • Vomiting

Certain drugs — including sibutramine (Meridia), which is used to treat obesity, and meperidine and tramadol (Ultram), which are usually given to reduce pain — may also raise serotonin levels in the body. If one of these drugs is used at the same time as tryptophan, the risk of serotonin syndrome may increase.

If tryptophan is taken with drugs in the benzodiazepine or phenothiazine classes, symptoms that resemble Parkinson's disease may result. Benzodiazepines such as alprazolam (Xanax) and diazepam (Valium) are usually used to treat anxiety. Phenothiazines such as chlorpromazine (Thorazine), prochlorperazine (Compazine), thioridazine (Mellaril), and trifluoperazine (Stelazine) may be used to treat mental disorders or vomiting. Parkinson's-like symptoms may include muscle stiffness, the inability to move quickly, and trembling.

Non-prescription Drugs

The sleep-producing effects of over-the-counter products containing diphenhydramine may be enhanced by taking tryptophan at the same time. Diphenhydramine is contained in many non-prescription sleeping pills as well as in some cough and cold products, therefore caution should be used when taking these medications with tryptophan because excessive drowsiness may result.

Dextromethorphan is an anti-coughing ingredient in many non-prescription cough and cold products such as Nyquil and Robitussin DM. Because it may have an increasing effect on serotonin levels, taking dextromethorphan with tryptophan may result in a higher risk of side effects.

Herbal Products

Tryptophan may cause excessive sedation if it is taken with potentially sedating herbs such as:

  • Catnip
  • Hops
  • Kava
  • St. John's Wort
  • Valerian

Potentially, if tryptophan is taken with another supplement or herbal, such as SAM-e or St John's wort, that also may increase serotonin levels, the risk of serotonin syndrome may increase.


No interactions between tryptophan and foods have been reported, but drinking alcohol at the same time as taking tryptophan may result in increased drowsiness.

Some interactions between herbal products and medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals.

Should I take it?

Tryptophan is one of the essential amino acids needed by humans - primarily to make proteins. Essential amino acids are necessary for body functions, but the human body cannot make them. They must be obtained from the diet in foods such as dairy products, eggs, fish, meats, and nuts. Commercial amino acid supplements commonly are derived from bacteria or plants; both of which do make essential amino acids. Supplemental tryptophan is made from purified bacteria by-products.

Tryptophan was first identified early in 1901 in a protein from milk. Nearly 70 years later, it was discovered to be involved in regulating appetite, mood, and sleep. Subsequently, tryptophan supplements were promoted for treating a number of conditions including depression, insomnia, and obesity. It was also thought to improve exercise capability, a theory that has not been proved. In 1989, a company that tried to increase their production of tryptophan, used a type of genetically modified bacteria. Over the next few years, suspected contaminants in the resulting tryptophan product caused more than 35 deaths and about 1500 cases of disability among individuals who took the product. Due to the severity of the reactions and the uncertainty about their exact cause, the FDA required all manufacturers of tryptophan to withdraw their products from the U.S. market. The only exceptions are medically-necessary foods and formulas that are given only under the supervision of a health professional.

Dosage and Administration

Although tryptophan is included in certain special dietary products, such as intravenous feedings and infant formulas, that are given with medical supervision; the use of tryptophan as a dietary supplement cannot be recommended.


The use of tryptophan as a dietary supplement cannot be recommended due to the slight possibility it may cause eosinophilia-myalgia syndrome that may result in death or permanent disability.


Eosinophilia-myalgia syndrome, a potentially life-threatening condition, has been attributed to taking tryptophan supplements. While investigations into the exact reasons for this association were made, the U.S. FDA removed most tryptophan supplements from the market in this country.

Pregnant and breast-feeding women and individuals who have kidney or liver diseases should be especially careful to avoid taking tryptophan supplements.

Side Effects

Documented cases of eosinophilia-myalgia syndrome have been associated with taking tryptophan supplements. Symptoms of this possibly fatal condition include:

  • Fever
  • Muscle and joint pain
  • Rash
  • Swelling in the face, arms, or legs

Less serious side effects such as blurry vision, drowsiness, muscle incoordination, and nausea may also be caused by supplemental tryptophan.


Because it promotes sleepiness, tryptophan may increase the sedation associated with certain prescription drugs, non-prescription drugs, herbals, dietary supplements, and alcohol. Taking tryptophan may increase the risk of a serious condition known as serotonin syndrome, if it is taken with SSRI antidepressants, sibutramine, the pain drugs meperidine or tramadol, dextromethorphan, or herbals such as SAM-e or St. John's wort. Tryptophan may increase the effect and side effects from MAOI antidepressants. If it is used with anti-anxiety drugs in the benzodiazepine class or anti-psychotic drugs in the phenothiazine class, tryptophan may cause shaking, muscle stiffness, and other symptoms that resemble Parkinson's disease.


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(Note: The above information is not intended to replace the advice of your physician, pharmacist, or other healthcare professional. It is not meant to indicate that the use of the product is safe, appropriate, or effective for you.)

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