5-OH-indoleacetic Acid (5-HIAA) is a downstream metabolite of serotonin, which is formed from the essential amino acid tryptophan. Most blood serotonin and urinary 5-HIAA comes from serotonin formation outside of the CNS, primarily the liver and enterochromaffin cells in the gastrointestinal tract. Serotonin is further metabolized by monoamine oxidase to become 5-HIAA.
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Decreased 5-HIAA levels can reflect low tryptophan intake, or malabsorption/maldigestion of tryptophan. Medications, like MAO inhibitors, decrease serotonin turnover and decrease 5-HIAA. Low levels of urinary 5-HIAA have been observed in cardiovascular disease, metabolic syndrome, IBS patients, and those with mood disorders and migraines.
Elevations, as well as low levels of urinary 5-HIAA, can reflect underlying intestinal microbial balance. Serotonin produced by intestinal enterochromaffin cells is necessary for GI motility. Because of this, antidepressants such as tricyclics and serotonin selective reuptake inhibitors have been used in treating IBS. Enterochromaffin cells and their serotonin signaling are influenced by overall inflammatory responses to bacteria in the GI tract. Diets rich in tryptophan and serotonin have been shown to increase urinary 5-HIAA. Bananas, plantains, kiwi, pineapple, nuts, and tomatoes, among other foods, can cause elevations of this urinary metabolite.
The excretion of 5-HIAA seems to vary among individuals who supplement with 5-hydroxytryptophan (5HTP). Carcinoid tumors are well-differentiated neuroendocrine tumors derived from the enterochromaffin cells in the GI tract and lung. These tumors secrete vasoactive peptides, especially serotonin which causes flushing and diarrhea. Urinary 5-HIAA levels are elevated in patients with carcinoid syndromes. It should be noted that certain medications may cause false abnormalities in urinary 5-HIAA, and/ or interfere with electrochemical detection on chromatography. These include guaifenesin, aspirin, and acetaminophen. Many medications can alter serotonin levels and therefore impact urinary 5-HIAA levels. Due diligence is recommended to investigate medications as a possible etiology of abnormal levels. Abnormalities, both high and low, in urinary 5-HIAA can be caused by methylation defects, as well as vitamin and mineral nutrient cofactor deficiencies
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