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Public Science Insights: Tryptophan in Chronic Kidney Disease: Should I Consume More Tryptophan?

Posted Thu, Mar, 09,2017

What is the role of a person’s kidneys? Two healthy kidneys continuously filter blood to form urine composed of unwanted fluid, vitamins, minerals and wastes such as toxins, chemicals, drugs. In addition, kidneys take vital role in making hormones and in the metabolism of nutrients such as carbohydrate (glucose) and amino acids (protein). 

One of the amino acids is tryptophan (TRP) – indispensable to humans for normal growth and energy production. Our body cannot make TRP and should be provided by food (or supplement). Interestingly, TRP is the least plentiful of all amino acids. TRP is found in most meat proteins as well as in egg, dairy products, soybeans, and seaweed. Turkey meat contains the highest amount of TRP. TRP is the precursor of serotonin – a neurotransmitter involve in appetite, sleep, mood, and other neurobehavioral functions. Therefore, many take TRP supplement as an antidepressant and sleep aid.

Our body uses about 5% of dietary TRP to make serotonin and the remainder is used in the kynurenine pathway to synthesize a host of neuroactive compounds or metabolites with myriad functions. Many of these toxic metabolites cannot cross from blood to brain through the blood-brain-barrier (BBB). Kynurenine pathway is tightly controlled by the immune system. Any imbalance in the pathway (for example high levels of metabolites during inflammation) may contribute to neurological disorders and psychiatric diseases such as Parkinson’s disease, Huntington’s disease, depression, schizophrenia, etc. 
 
So, what is the connection between TRP and kidney? It appears that healthy kidneys are vital to TRP metabolism and some of the metabolites in the kynurenine pathways are eliminated in the urine. When kidneys are damaged, they don't work properly causing buildup of several toxic metabolites including kynurenines in the body. In chronic kidney disease (CKD), kidney function starts declining and may eventually progress to chronic kidney failure requiring dialysis or kidney transplant. Most patients with chronic kidney failure or on dialysis experience depression, sleep disturbances, anxiety, impaired cognitive function and other symptoms and complications.
 
It is likely that many of these symptoms are due to low TRP levels and accumulation of toxic metabolites generated in the kynurenine pathway. Research in this area is limited and it is unknown if TRP supplement would alleviate any of these symptoms. If you have advanced CKD or chronic kidney failure or on dialysis, you should not consume too much animal protein or turkey meat without consulting your kidney doctor.
 
One may wonder how chronic kidney failure or dialysis treatment may cause all these symptoms. Available data indicate that CKD including chronic renal failure are inflammatory conditions and dialysis treatment may instigate inflammation. We have shown that in advanced CKD, normal pattern of TRP metabolism is altered – more TRP is broken down via the kynurenine pathway by the inflammatory cells. Dialysis treatment may disrupt the blood-brain-barrier. In addition, inflammatory cells are capable of disrupting the BBB, causing increased influx of neuroactive toxic kynurenine metabolites in the brain. Excess inflammatory cells and kynurenines in the brain may contribute to several disorders mentioned above.
 

Dr Subrata Debnath, MB.BS, MPH, PhD is the author of the recently published paper Tryptophan Metabolism in Patients with Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers, available for download now in International Journal of Tryptophan Research.

Bibliography: 
 
United States Department of Agriculture Food Composition Databases. https://ndb.nal.usda.gov/ndb/
 
Dawn M Richard, Michael A Dawes, Charles W Mathias, Ashley Acheson, Nathalie Hill-Kapturczak, and Donald M Dougherty. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int J Tryptophan Res. 2009; 2: 45-60.
 
Yiquan Chen and Gilles J. Guillemin. Kynurenine Pathway Metabolites in Humans: Disease and Healthy States. Int J Tryptophan Res. 2009; 2: 1-19.
 
Subrata Debnath, Chakradhar Velagapudi, Laney Redus, Farook Thameem, Balakuntalam Kasinath, Claudia E. Hura, Carlos Lorenzo, Hanna E. Abboud, Jason C. O'Connor. Tryptophan Metabolism in Patients with Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers. Int J Tryptophan Res. (in press)

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