5-HIAA, 5-hydroxyindoleacetic acid, is the primary metabolite of the breakdown of serotonin via the Monoamine Oxidase (MAO) enzyme. Through the lens of functional medicine, assessing 5-HIAA gives information on the activity of the MAO enzyme, which might provide insight into why a patient’s serotonin value is high or low. 5-HIAA is also tested as a way to diagnose and monitor carcinoid tumors. It is estimated that values >10 times the top of the reference range are suggestive of further work up for carcinoid tumor.
Carcinoid tumors are slow-growing noncancerous or cancerous neuroendocrine masses that can form in the GI tract, especially in the appendix, and in the lungs. According to the American Cancer Society, in the United States there are about 8,000 neuroendocrine tumors or cancers that start in the GI tract and 2,000 to 4,000 that start in the lungs diagnosed each year. While patients of any age can develop carcinoid tumors, the average age at diagnosis is usually in the early 60s.
About 10% of carcinoid tumors, primarily those found in the GI tract affecting the liver, will produce enough serotonin to cause symptoms, such as flushing of the face, diarrhea, a rapid heart rate, and wheezing, which are referred to as carcinoid syndrome. The serotonin that causes carcinoid syndrome may be released continuously or intermittently and can lead to significantly increased quantities of 5-HIAA in the blood and urine.
However, an elevated 5-HIAA level does not necessarily correspond with carcinoid tumor, as many substances can influence 5-HIAA levels. In any patient with elevated 5-HIAA, a thorough evaluation of diet, supplements, and medications that can increase serotonin and 5-HIAA should be conducted. Any and all of these should be avoided for 48 hours before a follow up test.
Foods to avoid (as they contain serotonin):
Pineapple and its juice
Tomatoes and all tomato products
Fruits in general
Nuts, especially walnuts
Medications that can increase 5-HIAA include acetaminophen, caffeine, ephedrine, diazepam (Valium®), fluorouracil, glyceryl guaiacolate (an ingredient found in some cough medicines), melphalan (Alkeran®), mephenesin, methamphetamine (Desoxyn), methocarbamol (Robaxin®), naproxen, nicotine, phenacetin, phenmetrazine, phenobarbital, phentolamine, rauwolfia, and reserpine.
Supplements that increase serotonin include tryptophan, 5-HTP, melatonin, and herbs like St. John’s Wort. Some evidence suggests that St. John’s Wort acts as an MAO Inhibitor, which would likely decrease the 5-HIAA level, but there may be additional mechanisms of action not yet understood that could impact 5-HIAA. Therefore, St John’s Wort and other serotonin supporting supplements should be avoided before a retest is indicated.
Research also suggests that urinary 5-HIAA levels can be increased in malabsorption syndromes, such as celiac disease and Whipple’s disease.
Additionally, in any patient with an elevated 5-HIAA level, screen for symptoms of carcinoid syndrome. Is the patient exhibiting flushing, diarrhea, abdominal pain, nausea or vomiting, wheezing, coughing, difficulty breathing, or a rapid heart rate? If not, this finding is more likely to be incidental.
Any elevation in 5-HIAA should be confirmed by repeat testing. If the 5-HIAA value does confirm with repeat testing, remember that a significantly increased level of 5-HIAA when you have carcinoid syndrome symptoms is suggestive but not diagnostic of a carcinoid tumor. In order to diagnose the condition, the tumor itself must be located, biopsied, and examined by a pathologist. A referral to an endocrinologist would be warranted.