Arginine, a naturally occurring amino acid, showed promise in preventing amyloid fibril formation by stabilizing the transthyretin (TTR) protein in its functional tetrameric form, according to a study published recently in Biochemical and Biophysical Research Communications.
The result suggested that arginine could be a safe and cost-effective supplement to delay or prevent the onset of transthyretin amyloidosis cardiomyopathy (ATTR-CM). The study highlighted arginine’s potential as a prophylactic option, offering hope for those at risk of this rare but serious condition.
What is ATTR-CM?
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare progressive disease of the heart muscle that leads to congestive heart failure. It occurs when the transthyretin protein produced by the liver is unstable. Symptoms include fatigue; shortness of breath; irregular heart rate or palpitations; swelling of the legs, ankles and stomach; brain fog; wheezing; and dizziness. It often goes underdiagnosed because of a lack of awareness and knowledge of the disease. There is currently no cure for ATTR-CM.
“Gene-silencing therapies and tetrameric TTR stabilizers effectively suppress ATTR progression; however, they are unsuitable for prophylactic treatment,” the study authors said. “This study demonstrated the potential of arginine, an inexpensive and safe amino acid, to overcome the limitations of current prophylactics, highlighting it as a new therapeutic option for ATTR.”
Read more about prognosis and staging of ATTR-CM
Researchers investigated arginine’s ability to inhibit the breakdown of TTR tetramers into monomers, a critical step in the formation of harmful amyloid fibrils. Laboratory experiments revealed that arginine significantly increased the tetramer-to-monomer ratio of both normal TTR and the mutant form associated with hereditary ATTR. Higher concentrations yielded greater stabilization.
The study also evaluated arginine’s effect on amyloid fibril formation using a Thioflavin T test, a method for detecting protein aggregation. Results showed that arginine suppressed the formation of amyloid fibrils in a dose-dependent manner. The findings were consistent when applied to human serum, further supporting its stabilizing effects on TTR.
To explore arginine’s real-world applicability, researchers administered 5,000 mg of arginine daily to healthy volunteers for five days. The treatment increased the tetramer-to-monomer ratio in their blood, demonstrating arginine’s effectiveness in stabilizing TTR within the human body. The result aligned with in vitro findings and underscored the potential for arginine as a noninvasive and affordable intervention.
ATTR, caused by the accumulation of amyloid fibrils, leads to progressive damage to various organs, including the heart and nerves. Current treatments target advanced stages and can be expensive, limiting access for many patients. Arginine’s safety profile and availability position it as an attractive option for preventing the early stages of ATTR.