The potential risks of excessive intake of L-isoleucine

L-isoleucine is an essential amino acid that offers benefits when consumed in appropriate amounts. However, excessive intake may pose a series of potential risks to kidney function, detailed as follows:

I. Increased Renal Metabolic Burden

1. Elevated Protein Metabolites

L-isoleucine participates in protein synthesis and metabolism in the body. When ingested in excess, the body cannot metabolize and utilize the surplus amino acids in a timely manner, leading to increased production of protein metabolites such as urea and creatinine. The kidneys must filter these waste products from the blood for excretion. A prolonged overload of metabolites significantly intensifies the kidneys' workload, potentially causing gradual damage to their structure and function over time.

2. Increased Glomerular Filtration Pressure

To eliminate the excess metabolites, the kidneys increase glomerular filtration rate, which raises intraglomerular pressure. Sustained high pressure can damage the glomerular filtration membrane, altering its permeability and impairing normal filtration function. Over time, this may trigger renal pathologies such as glomerulosclerosis.

II. Disruption of Renal Internal Environment Stability

1. Acid-Base Imbalance

L-isoleucine produces acidic substances during metabolism. Excessive intake leads to an accumulation of acids in the body, disrupting the acid-base balance maintained by the kidneys. While the kidneys regulate the excretion and reabsorption of acid-base substances to stabilize pH, an overwhelming acid load can exceed their regulatory capacity, causing metabolic acidosis. Chronic metabolic acidosis impairs normal renal function and further damages renal tubules and interstitium.

2. Electrolyte Disorders

Excessive L-isoleucine intake may interfere with renal reabsorption and excretion of electrolytes (e.g., sodium, potassium, calcium, phosphorus). Imbalances in these electrolytes negatively affect renal cell function and disrupt normal renal physiology. For example, hypernatremia may cause renal water-sodium retention and increase kidney burden, while hypokalemia may impair tubular concentration and dilution abilities.

III. Induction of Renal Inflammation and Fibrosis

1. Oxidative Stress and Inflammatory Response

Excessive L-isoleucine intake can elevate oxidative stress levels in the body, generating an excess of reactive oxygen species (ROS). These ROS cause oxidative damage to renal cells and trigger inflammatory responses. Infiltration of inflammatory cells and release of inflammatory mediators further damage renal tissues, disrupting their normal structure and function. Prolonged inflammation may also promote the development of renal fibrosis.

2. Renal Interstitial Fibrosis

Sustained oxidative stress and inflammation stimulate the activation and proliferation of renal interstitial fibroblasts, leading to increased synthesis and reduced degradation of extracellular matrix (ECM). This ultimately results in renal interstitial fibrosis, which progressively destroys normal renal tissue structure, reduces effective filtration area, impairs renal blood perfusion and function, and may advance to renal failure in severe cases.

IV. Increased Risk of Urinary System Calculi

Abnormal Oxalate Metabolism

Excessive L-isoleucine intake may disrupt oxalate metabolism in the body. Oxalate is a common component of kidney stones; elevated oxalate concentrations readily bind with calcium ions to form calcium oxalate stones. As the primary organ for oxalate excretion, the kidneys may suffer from deposition of excess calcium oxalate crystals, which damage renal tubular epithelial cells, cause tubular obstruction and inflammation, and increase the risk of urinary calculi. The presence of stones further impairs renal function, leading to complications such as hydronephrosis and infection.