Kynurenate (Male)
Kynurenate is product of the metabolism of L-Tryptophan and appears in urine in Vitamin B6 deficiencies. Your body needs vitamin B6 (pyridoxine) to utilize amino acids derived from dietary protein. Inadequate vitamin B6 is one factor that leads to increased concentrations of kynurenate and xanthurenate in urine. These products of amino acid breakdown cannot be further metabolized in the absence of vitamin B6.
Xanthurenate and kynurenate are metabolic byproducts in the production of tryptophan to NAD in the liver. If either xanthurenate or kynurenate build up in the urine, it can indicate a need for vitamin B6. This need is amplified if BOTH markers are elevated, and often indicates a more severe deficiency of vitamin B6. Vitamin B6 is critical as a co-factor to over 100 important reactions that occur in the human body and is stored in the highest concentration in muscle tissue.
Tryptophan is converted to NAD by the liver and one of the steps in this pathway requires B6. When B6 is insufficient, xanthurenate is made instead. Xanthurenate can also bind to iron and create a complex that increases DNA oxidative damage resulting in higher 8-OHdG levels. If both the xanthurenate and 8OhdG levels are elevated, there is likely an antioxidant insufficiency.
Kynurenate may also become elevated when patients are B6 deficient because of a different, possibly less B6 dependent pathway. While there is always some tryptophan going down the kynurenine pathway towards NAD, and possibly xanthurenate, this process is up regulated by inflammation, estrogen and cortisol elevations. If levels of estrogen or cortisol are high, it may exacerbate kynurenic acid and increase the need for vitamin B6. As the Xanthurenate and Kynurenate pathways lead to biomarkers with other influence in the body, elevations in these markers may not always agree.
What does it mean if your Kynurenate (Male) result is too high?
- A high reading of this by-product of the breakdown of the amino acid tryptophan is consistent with a vitamin B6 deficiency, possible inflammatory processes, interferon-gamma stimulated macrophages or excessive tryptophan supplementation (not 5-HTP).
- Abnormally high levels can cause and increase in pain sensations and may, in multiple sclerosis patients, be a marker for an exacerbation period.
- Vitamin B6 deficiency may also result in elevated concentrations of homocysteine in blood, which leads to increased risk of heart disease.
- High levels of kynurenate can have direct effects on brain function in addition to showing a need for vitamin B6.
- High values in individuals with the yeast overgrowth syndrome may be due to yeast interference.
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Kynurenate is a product of tryptophan metabolism and can elevate if there is a B6 deficiency, chronic stress, higher levels of reactive oxygen species (ROS), inflammation and possibly Lipopolysaccharides (LPS) from gram negative bacteria in the gut (such as with leaky gut).
It may also elevate when patients are on a ketogenic diet. Foods, including white potatoes, bee products (honey, propolis, etc), fresh broccoli, basil and thyme will also elevate this marker.
Elevated levels have also been found in schizophrenia, Alzheimer’s, cluster headaches (= excruciating attacks of pain in one side of the head, often felt around the eye), chronic migraines and psychosis (= a collection of symptoms that affect the mind, where there has been some loss of contact with reality).
While there is always some tryptophan going down the kynurenine pathway towards NAD (and possibly xanthurenate), this process is up regulated by inflammation, estrogen elevations and high cortisol. If levels of estrogen or cortisol are high, it may exacerbate xanthurenate and kynurenate elevations and increase the need for B6.
→ Although kynurenate can be helpful in the body, as it can act as an anti-inflammatory agent and has some anti-ulcer properties, its influence is dependent on dose and length of exposure.
→ Too much kynurenate can decrease glutamate but can also inhibit alpha-y-nicotinic acetylcholine, leading to less acetylcholine and likely less dopamine.
→ When levels are elevated, make sure to rule out any underlying inflammation and lower inflammation first and foremost.
→ Consider support of this pathway with vitamin B6, especially if xanthurenate is also elevated, in addition to antioxidants including vitamin C, vitamin E, ALA, magnesium and taurine. Other support includes considering huperzine A or the medication of choice is Galantamine.
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