Protein toxicity is the effect of the buildup of protein metabolic waste compounds, like urea, uric acid, ammonia, and creatinine. Protein toxicity has many causes, including urea cycle disorders, genetic mutations, excessive protein intake, and insufficient kidney function, such as chronic kidney disease and acute kidney injury. Symptoms of protein toxicity include unexplained vomiting and loss of appetite. Untreated protein toxicity can lead to serious complications such as seizures, encephalopathy, further kidney damage, and even death. One form of protein toxicity, called "protein poisoning" or "rabbit starvation", was described by arctic explorer Vilhjalmur Stefansson as occurring when a person survives on lean animals such as rabbit, without consuming sufficient fats or carbohydrates over an endured period. This form of acute malnutrition results from a very high proportion of dietary protein rather than a lack of calories, despite adequate food intake.
Definition Protein toxicity occurs when protein metabolic wastes build up in the body. During protein metabolism, nitrogenous wastes such as urea, uric acid, ammonia, and creatinine are produced. These compounds are not utilized by the human body and are usually excreted by the kidney. However, due to conditions such as renal insufficiency, the under-functioning kidney is unable to excrete these metabolic wastes, causing them to accumulate in the body and lead to toxicity. Although there are many causes of protein toxicity, this condition is most prevalent in people with chronic kidney disease who consume a protein-rich diet, specifically, proteins from animal sources that are rapidly digested and metabolized, causing the release of a high concentration of protein metabolic wastes in the blood stream rapidly.
Causes and pathophysiology Protein toxicity has a significant role in neurodegenerative diseases, whether it is due to high protein intake, pathological disorders leading to the accumulation of protein waste products, the inefficient metabolism of the proteins, or oligomerization of the amino acids from proteolysis. The mechanism by which protein can lead to well known neurodegenerative diseases includes transcriptions dysfunction, propagation, pathological cytoplasmic inclusions, mitochondrial and stress granule dysfunction. Ammonia, one of the waste products of protein metabolism, is very harmful, especially to the brain, where it crosses the blood brain barrier leading to a whole range of neurological dysfunctions from cognitive impairment to death. The brain has a mechanism to counteract the presence of this waste metabolite. One of the mechanisms involved in the impairment of the brain is the compromise of astrocyte potassium buffering, where astrocytes play a key role. However, as more ammonia crosses, the system gets saturated, leading to astrocyte swelling and brain edema. Urea is another waste product that originates from protein metabolism in humans. However, urea is used by the body as a source of nitrogen essential for growth and life. The most relevant disorders on the urea cycle are genetic, leading to defective enzymes or transporters inhibiting the reabsorption of urate with the subsequent increase in levels of ammonia, which is toxic. High protein intake can lead to high protein waste, and this is different from protein poisoning since the issue relates to the high level of the waste metabolites. Usually, when protein consumption goes above one-third of the food we consumed, this situation presents. The liver has a limited capacity and will not deaminate proteins, leading to increased nitrogen in the body. The rate at which urea is excreted can not keep up with the rate at which it is produced. The catabolism of amino acids can lead to toxic levels of ammonia. Furthermore, there is a limited rate at which the gastrointestinal tract can absorb amino acids from proteins. Uric acid is not a waste metabolite derived from protein metabolism, but many high protein diets also contain higher relative fractions of nucleic acids. One of the two types of nucleic acids, purines (the other being pyrimidines, which are not problematic), are metabolized to uric acid in humans when in excess, which can lead to problems, chiefly gout. The kidneys play an essential role in the reabsorption and excretion of uric acid. Certain transporters located in the nephron in the apical and basolateral surfaces regulate uric acid serum levels. Uric acid is not as toxic as other nitrogen derivates. It has an antioxidant function in the blood at low levels. People with compromised kidneys will have a lower excretion of uric acid leading to several diseases, including further renal damage, cardiovascular disease, diabetes, and gout. Creatinine might not be a direct indicator of protein toxicity; however, it is important to mention that creatinine could increase due to overwork by the kidneys exposed to high levels of protein waste. Also, high serum creatinine levels could indicate decreased renal filtration rate due to kidney disease, increase byproduct as a consequence of muscle breakdown, or high protein intake.
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