5-Hydroxyindoleacetate

Urine
Optimal Result: 1.17 - 8.06 ug/mg creatinine.

5-Hydroxyindoleacetic acid (5HIAA) is a breakdown product of serotonin that is excreted in the urine. Serotonin is a hormone found at high levels in many body tissues. Serotonin and 5HIAA are produced in excess amounts by carcinoid tumors, and levels of these substances may be measured in the urine to test for carcinoid tumors.

5-Hydroxyindoleacetic acid is found to be associated with:

- Aromatic l-amino acid decarboxylase deficiency an inherited disorder that affects the way signals are passed between certain cells in the nervous system.)

- Celiac disease (an autoimmune disorder where the ingestion of gluten leads to damage in the small intestine)

- Sepiapterin reductase deficiency (a condition characterized by movement problems)

- What are normal levels?

Normal results are 3 to 15 milligrams (mg) of 5-HIAA over 24 hours.

Women generally have lower levels than men.

Numerous drugs affect the excretion of 5-HIAA by different mechanisms, including increased serotonin synthesis, metabolism, and release and inhibition of uptake. The following medications can interfere with 5-HIAA results. Proper preparation before the test is essential. Medication and dietary restrictions are required to prevent false-positive results. If clinically feasible, discontinue the following medications at least 48 hours before specimen collection. 

- Acetaminophen (Tylenol or generic versions)

- Aspirin

- Antihistamines

- Cough syrups

- Cold and flu medications

One should also avoid caffeinated beverages such as tea and coffee or caffeinated foods for 48 hours before and during specimen collection.

Certain medicines can raise or lower your 5-HIAA levels. These include:

- Aspirin

- Acetaminophen

- Ethyl alcohol

- Some antidepressants

- Cough medicines or antihistamines

- Medicines to relax muscles

References:

- Urinary sampling for 5HIAA and metanephrines determination: revisiting the recommendations, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527357/

- Guidelines for the diagnosis and management of carcinoid tumours. Part 1: the gastrointestinal tract. A statement from a Canadian National Carcinoid Expert Group. (https://www.ncbi.nlm.nih.gov/pubmed/17576444)

- A single fasting plasma 5-HIAA value correlates with 24-hour urinary 5-HIAA values and other biomarkers in midgut neuroendocrine tumors (NETs). (https://www.ncbi.nlm.nih.gov/pubmed/23160483)

- Aromatic l-amino acid decarboxylase deficiency, https://ghr.nlm.nih.gov/condition/aromatic-l-amino-acid-decarboxylase-deficiency

- WHAT IS CELIAC DISEASE?, https://celiac.org/celiac-disease/understanding-celiac-disease-2/what-is-celiac-disease/

- Sepiapterin reductase deficiency, https://ghr.nlm.nih.gov/condition/sepiapterin-reductase-deficiency

What does it mean if your 5-Hydroxyindoleacetate result is too low?

Low levels of 5-hydroxyindolacetate may occur if there are nutritional enzyme inhibitions or inherited low-activity enzyme variants present in the breakdown pathway, or if there are low levels of its precursor serotonin. Serotonin is derived from the essential amino acid tryptophan and is essential for normal neurotransmission in the central nervous system and the gastrointestinal (enteric) nervous system. Serotonin also regulates the dilation and constriction of blood vessels and plays a role in immune system and bone health. The breakdown of peripheral serotonin occurs primarily in the liver; low levels of 5-hydroxyindolacetate and vanilmandelate may indicate the presence of a liver disorder. Support either serotonin synthesis or breakdown depending upon symptoms.

1. Low levels of serotonin have been associated with obsessive-compulsive disorder (OCD), aggression, insomnia, fibromyalgia, rheumatoid arthritis, and depression. Eating disorders and migraine headaches may also be related to low serotonin levels. If appropriate, consider supporting serotonin synthesis with vitamin B6, D, iron (if deficient) and tetrahydrobiopterin (BH4). Tryptophan or 5-hydroxytryptophan (5-HTP) may be used to supply substrate, and tryptophan may be given on an empty stomach to increase absorption and decrease transporter competition by other amino acids. Digestive disorders may decrease tryptophan absorption. Consider a US BIOTEK VITAMIN D PROFILE (serum or dried bloodspot).

2. High levels of serotonin in the central nervous system may result in cognitive changes/confusion, restlessness, headaches, GI hypermotility, tachycardia, agitation, and may contribute to schizophrenia. Diets high in simple carbohydrates may increase serotonin levels. The use of tryptophan or 5-HTP supplements, insulin and certain medications may also increase serotonin levels. High serotonin levels may occur if there is an enzymatic block in melatonin synthesis. If appropriate, consider supporting serotonin breakdown with vitamins B2, B3, iron (if deficient), and molybdenum. If insomnia or sleep disorders are present, consider melatonin supplementation.

What does it mean if your 5-Hydroxyindoleacetate result is too high?

High levels of 5-hydroxyindoleacetate may occur if there are inherited high-activity enzyme variations on the breakdown pathway or if there are higher levels of its precursor serotonin. A higher rate of serotonin breakdown may decrease serotonin levels while 5-hydroxyindoleacetate levels remain high.

- Low levels of serotonin have been associated with obsessive-compulsive disorder (OCD), aggression, insomnia, fibromyalgia, rheumatoid arthritis and depression. Eating disorders and migraine headaches may also be related to low serotonin levels. If appropriate, consider slowing serotonin breakdown with selenium and antioxidant support. Antioxidant supports may include CoQ10, alpha-lipoic acid, vitamins C and E, curcumin, resveratrol, etc. Fresh fruits and vegetables are rich in antioxidant compounds. Increased levels of methylmalonate, quinolinate and pyroglutamate, with decreased levels of cis-aconitate and isocitrate, can indicate poor antioxidant status. If appropriate, consider supporting serotonin synthesis with vitamin B6, D, iron (if deficient) and tetrahydrobiopterin (BH4). Tryptophan or 5-hydroxytryptophan (5-HTP) may be used to supply substrate and tryptophan may be given on an empty stomach to increase absorption and decrease transporter competition by other amino acids.

- High levels of serotonin in the central nervous system may result in cognitive changes/confusion, restlessness, headaches, GI hypermotility, tachycardia, agitation, and may contribute to schizophrenia. Diets high in simple carbohydrates may increase serotonin levels. The use of tryptophan or 5-HTP supplements, insulin and certain medications may also increase serotonin levels. High serotonin levels may also occur if there is an enzymatic block in melatonin synthesis. If appropriate, consider supporting serotonin breakdown with vitamins B2, B3, iron (if deficient), and molybdenum. If insomnia or sleep disorders are present, consider melatonin supplementation.

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