How to Test for Serotonin Levels

Serotonin, scientifically known as 5-hydroxytryptamine (5-HT), functions as both a neurotransmitter in the brain and a hormone throughout the body. The majority of the body’s serotonin, approximately 90%, is found in the gastrointestinal tract, where it regulates gut motility and digestion. While serotonin is widely recognized for its role in regulating mood, sleep, and appetite within the central nervous system, standard clinical testing is rarely ordered to assess general mental health conditions like depression or anxiety. Instead, measuring serotonin levels is primarily a diagnostic tool reserved for identifying specific physical disorders involving the overproduction of this chemical.

Clinical Reasons for Serotonin Testing

A physician typically orders serotonin testing when a patient presents with symptoms suggesting a rare condition that causes an abnormal, systemic increase in the chemical’s production. The most common medical context for this testing is the diagnosis and monitoring of carcinoid tumors. These are slow-growing neuroendocrine tumors that often originate in the gastrointestinal tract or lungs.

When these tumors, particularly those that have spread to the liver, produce and secrete excessive amounts of serotonin into the bloodstream, they can cause a collection of symptoms known as carcinoid syndrome. These symptoms include severe skin flushing, chronic diarrhea, and sometimes wheezing or heart valve damage. Testing is used to confirm the presence of this abnormal serotonin secretion.

Serotonin in the brain cannot be accurately measured by a simple blood or urine test because it is separated from the bloodstream by the blood-brain barrier. Therefore, a low result from a peripheral test does not confirm a diagnosis of a mood disorder. For this reason, the tests are considered a specialized tool for specific physical diseases, not a general screen for psychological well-being.

Standard Serotonin Measurement Techniques

To assess the body’s overall serotonin output, two main laboratory tests are utilized. The most widely used diagnostic test is the 24-hour urine 5-HIAA test, which measures 5-hydroxyindoleacetic acid (5-HIAA). 5-HIAA is the primary breakdown product, or metabolite, created by the liver after metabolizing serotonin, which is then excreted in the urine.

Collecting urine over a full 24-hour period is considered the most reliable method because it accounts for the normal daily fluctuations in serotonin production and excretion. A blood serotonin test, measuring the chemical directly in the serum or plasma, is sometimes used as an alternative or supplementary test.

The blood test primarily measures the serotonin released by blood platelets, where it is stored after being absorbed from the gut. While it is quicker and more convenient than a 24-hour collection, the blood test is considered less specific for diagnosing carcinoid syndrome.

Preparing for Accurate Test Results

Strict patient preparation is required for accurate serotonin testing, particularly the 5-HIAA urine test. Since many common foods contain high levels of serotonin or its precursors, consuming them can lead to a false positive result. Patients are typically instructed to avoid specific foods for at least three days prior to and during the collection period.

Foods to avoid often include items that can artificially elevate the measured 5-HIAA level:

  • Bananas
  • Pineapples
  • Plums
  • Avocados
  • Walnuts
  • Eggplant
  • Tomatoes

A number of medications can also interfere with the test results by altering serotonin metabolism or by chemically interfering with the laboratory assay. Drugs that may need to be temporarily stopped include:

  • Certain cough medicines containing guaifenesin
  • Muscle relaxants like methocarbamol
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Monoamine oxidase inhibitors (MAOIs)

Patients must consult with their physician before discontinuing any prescribed medication, as suddenly stopping certain drugs can have serious health consequences.

Interpreting High and Low Levels

A significantly elevated level of 5-HIAA in the 24-hour urine test is a strong indicator of a functional neuroendocrine tumor. When combined with the physical symptoms of flushing and diarrhea, these high results help confirm the diagnosis of carcinoid syndrome. Consistently high levels during monitoring can also indicate a lack of response to treatment or disease progression.

A result that falls below the established reference range is rarely used as a stand-alone diagnostic tool for mood disorders. While low serotonin activity in the brain has been theoretically linked to conditions like depression, a low peripheral result from a blood or urine test does not translate directly to a lack of serotonin in the central nervous system.