This is the ratio of Quinolinic acid (QA, a tryptophan metabolite), and 5-hydroxyindoleacetic acid (5-HIAA, a serotonin metabolite).
5-Hydroxyindolacetic 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.
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.
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.
Quinolinic acid is a tryptophan metabolite formed through the kynurenine pathway. Tryptophan is the amino acid precursor to serotonin; its major route for catabolism is the kynurenine pathway. Important products of the kynurenine pathway include xanthurenic acid and kynurenic acid, which can further metabolize into quinolinic acid. The historical importance of this pathway has mainly been as a source of the coenzyme NAD+, which is important for all redox reactions in the mitochondria. However, it is now understood that kynurenic and quinolinic acid have physiologic implications. This alternate pathway is upregulated in response to inflammation and stress, which can lead to deficient serotonin production. Kynurenic acid has shown some neuroprotective properties in the brain, since it can stimulate NMDA receptors. However, its importance on the periphery is still not fully elucidated. Some studies outline anti-inflammatory, analgesic, antiatherogenic, antioxidative, and hepatoprotective properties to peripheral kynurenic acid. The correlation to levels of urinary excretion needs further study. Quinolinic acid, in and of itself, can be inflammatory and neurotoxic.
The kynurenine pathway is particularly sensitive to vitamin B6 deficiency, which can elevate urinary kynurenic acid (and xanthurenic acid).
Vitamin B2 is also an important vitamin cofactor in the enzymatic conversion reactions within the pathway. Because a major-end product of this pathway is also NAD+, elevations in kynurenic and quinolinic acid may also reflect vitamin B3 need. Oral contraceptives and estrogen therapy have been implicated in increasing quinolinic acid excretion both from altered tryptophan metabolism directly, as well as vitamin B6 insufficiency. Many of the intermediates and products in the kynurenine pathway are implicated in numerous neurological and psychiatric diseases, such as depression. Alterations in this pathway also have some connection to the development of insulin resistance, diabetes, tumor growth and proliferation, and inflammatory myopathies.
A high ratio of quinolinic acid to the tryptophan metabolite, 5-hydroxyindoleacetic acid, indicates excessive inflammation due to recurrent infections, excessive tryptophan intake, immune overstimulation, excessive adrenal production of cortisol, or excessive exposure to phthalates.
Quinolinic acid/5-HIAA Ratio
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