Quinolinic

Optimal Result: 0.85 - 3.9 mmol/mol creatinine.

Quinolinic acid is a neurotoxic substance produced by our own bodies and a metabolite of tryptophan.

Tryptophan and its different pathways:

The management of tryptophan converting to serotonin within the brain has some complex moving parts. Tryptophan gets converted into serotonin. High levels of stress of any type and acute/chronic infections can change this process by provoking an immune system response. Instead of serotonin being made from tryptophan in this process, two other compounds are eventually made: They are kynurenic acid which is neuroprotective and quinolinic acid which is neurodegenerative.The quinolinic acid is a NMDA-agonist, i.e. quinolinic acid, NMDA, and inflammation are best friends and like to wreak havoc when kynurenic acid is lacking. Recent research showed that patients suffering from severe depression and suicidality were found to have very high levels of inflammation and elevated NMDA activity as a result of long-term dysregulation of this pathway. The researchers’ recommended goal was to find ways to dampen the NMDA receptors and quinolinic acid in the brain.

Treatment:

The cause of inflammation needs to be treated. Simply taking SSRI drugs (Selective serotonin reuptake inhibitors) to make more serotonin further downstream is not going to work. The drug use and application generally fails to address the inflammation. The drugs simply try to increase the amount of serotonin within the system at the synapses, but the underlying damaging inflammation is still ongoing. This process also affects cognitive health, which has great implications for all neurodegenerative concerns. When the brain is on fire with inflammation leading to depression, anxiety, sleep problems, cognitive changes, it has to be thoroughly addressed. SSRIs miss this inflammatory aspect.

Resources:

- NMDA receptor function, memory, and brain aging (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181613/)

- A mechanism of quinolinic acid formation by brain in inflammatory neurological disease. Attenuation of synthesis from L-tryptophan by 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate. (https://www.ncbi.nlm.nih.gov/pubmed/8293279)

- Sulforaphane reduces the alterations induced by quinolinic acid: Modulation of glutathione levels (https://www.researchgate.net/publication/262569040_Sulforaphane_reduces_the_alterations_induced_by_quinolinic_acid_Modulation_of_glutathione_levels)

- Protective effects of the antioxidant selenium on quinolinic acid-induced neurotoxicity in rats: in vitro and in vivo studies. (https://www.ncbi.nlm.nih.gov/pubmed/12871589)

- Melatonin neutralizes neurotoxicity induced by quinolinic acid in brain tissue culture. (https://www.ncbi.nlm.nih.gov/pubmed/16150107)

- Neuroprotective potential of L-theanine against excitotoxic neuronal death induced by quinolinic acid: Possible neurotransmitters and nitric oxide modulation mechanism (http://www.mdsabstracts.org/abstract/neuroprotective-potential-of-l-theanine-against-excitotoxic-neuronal-death-induced-by-quinolinic-acid-possible-neurotransmitters-and-nitric-oxide-modulation-mechanism/)

- Green Tea Polyphenols Decrease Enzyme Activity of Nitric Oxide Synthase, https://www.fasebj.org/doi/abs/10.1096/fasebj.27.1_supplement.790.14

- Neuroprotective Activity of Curcumin in Combination with Piperine against Quinolinic Acid Induced Neurodegeneration in Rats (https://www.karger.com/Article/PDF/443896)

What does it mean if your Quinolinic result is too high?

High levels might be associated with mental illness, ALS, alzheimer's and depression. Studies have demonstrated that quinolinic acid may be involved in many psychiatric disorders, neurodegenerative processes in the brain, as well as other disorders such as mental illness, ALS, alzheimer's and depression.

Brain toxicity due to quinolinic acid has also been implicated in autism, Huntington’s disease, stroke, dementia of old age, depression, HIV-associated dementia, and schizophrenia.

Increased levels of quinolinic acid have also been detected in Lyme patients with central nervous system inflammation.

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High quinolinic acid may be a sign of inflammation and/or neural excitotoxicity. Quinolinic acid is derived from the amino acid tryptophan and is neurotoxic at high levels. As an excitotoxic stimulant of certain brain cells that have NMDA-type receptors, high quinolinic acid may cause nerve cell death with continuous stimulation.

High levels of quinolinic acid may inhibit heart contractions, cause lipid peroxidation in the brain, and increase apoptosis (programmed cell death) of astrocytes in human brain. The level of quinolinic acid is also highly correlated with the degree of arthritis impairment.

Quinolinic acid is also a metal chelator, and inhibits enzymes that allow the body to produce glucose when needed. Excessive immune stimulation and chronic inflammation, resulting in overproduction of cytokines like interferon, stimulates overproduction of quinolinic acid. However, quinolinic acid is an important intermediate in making the essential nutritional cofactor nicotinamide adenine dinucleotide (NAD), which is also derived from niacin (B3). Phthalates inhibit the conversion of quinolinic acid to NAD.

Treatment of excessive levels of quinolinic acid can be achieved by multiple approaches:

- reducing tryptophan supplements,

- preventing repeated infections and subsequent immune overstimulation by: supplementation with colostrum, transfer factor and probiotics;

- reducing the use of immune modulators like interferon that increase quinolinic acid production;

- or reducing the numbers of vaccines given at one time or increasing the interval between vaccinations.

- The dietary supplements B6 (pyridoxine) and magnesium may reduce brain damage caused by quinolinic acid.

A high quinolinic acid/ 5-hydroxyindoleacetic acid ratio would be indicative of immune overstimulation and/or phthalate toxicity.

In addition to the above, the following substances have been proven to lower levels of quinolinic acid:

- Sulforaphane [R]

- Selenium [R]

- Melatonin [R]

- Theanine [R]

- Green Tea Polyphenols [R]

- Curcumin + Piperine [R]

What does it mean if your Quinolinic result is too low?

High levels might be associated with mental illness, ALS, alzheimer's and depression. Studies have demonstrated that quinolinic acid may be involved in many psychiatric disorders, neurodegenerative processes in the brain, as well as other disorders such as mental illness, ALS, alzheimer's and depression.

Increased levels of quinolinic acid have also been detected in Lyme patients with central nervous system inflammation.

The following substances have been proven to lower levels of quinolinic acid:

- Sulforaphane [R]

- Selenium [R]

- Melatonin [R]

- Theanine [R]

- Green Tea Polyphenols [R]

- Curcumin + Piperine [R]

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