The bioavailability of L-Arginine and its influencing factors

The bioavailability of L-Arginine refers to the proportion of it that is absorbed, transported, and involved in metabolic reactions after being ingested orally or through other routes. It is a key indicator for measuring the efficiency of its physiological functions (such as nitrogen metabolism and nitric oxide synthesis). Its bioavailability is affected by various factors including the mode of intake, body state, dietary interactions, and metabolic characteristics, which are analyzed in detail as follows:

I. Basic Impact of Intake Methods and Absorption Processes on Bioavailability

Absorption limitations of oral administration: After oral intake of L-Arginine, it is mainly absorbed in the small intestine through active transport (relying on amino acid transporters b⁰⁺AT and y⁺LAT1). However, there is a "first-pass effect" — some unabsorbed arginine will be decomposed into ornithine, citrulline, or ammonia by intestinal flora, resulting in a reduction in the effective amount entering the systemic circulation (bioavailability is usually 50%-70%).

Advantages of parenteral routes: In intravenous injection, arginine can directly enter the blood, avoiding intestinal metabolic loss, and its bioavailability is close to 100%. However, the dose must be strictly controlled (excess may cause hyperammonemia), so it is only used in clinical scenarios where oral administration is impossible (such as postoperative nutritional support).

II. Dynamic Regulatory Role of Body Metabolic Status

Balance between endogenous synthesis and demand: The human body can synthesize arginine from ornithine through the urea cycle (mainly in the kidneys). When endogenous synthesis is sufficient (such as in healthy adults), the bioavailability of exogenously ingested arginine will decrease — arginase in the liver will accelerate its decomposition into urea and ornithine to maintain nitrogen balance in the body. At this time, only part of the orally supplemented arginine can reach peripheral tissues (such as vascular endothelial cells and immune cells). Conversely, during trauma, infection, or the growth and development period, the body's demand for arginine surges, and endogenous synthesis is insufficient. The decomposition of exogenously ingested arginine decreases, and its bioavailability can increase to more than 80%.

Genetic and enzymatic activity differences: Gene polymorphisms of arginase or related transporters can affect metabolic efficiency. For example, patients with arginase deficiency cannot effectively decompose arginine, and exogenous intake is prone to accumulation in the body, making bioavailability seem to increase, but in fact, it may cause toxicity. For those with weakened transporter function, intestinal absorption efficiency decreases, and even with high-dose intake, the systemic circulation concentration is difficult to increase.

III. Synergistic and Interfering Effects of Dietary Components

Competitive inhibition by other amino acids: Arginine shares intestinal transporters with basic amino acids such as lysine and ornithine. If high-dose lysine is ingested at the same time (such as in meat and beans in a high-protein diet), it will competitively inhibit the absorption of arginine, resulting in a 10%-30% reduction in its bioavailability. On the contrary, when taken together with neutral amino acids such as glutamine and proline, there is no obvious competition, and it may even indirectly improve absorption efficiency by promoting intestinal mucosal repair.

Dual role of dietary fiber and flora: Water-soluble dietary fiber (such as pectin and inulin) can delay intestinal emptying, prolong the absorption time of arginine, and improve its bioavailability; however, excessive insoluble dietary fiber (such as wheat bran) may adsorb arginine, reducing its contact with the intestinal mucosa and decreasing absorption. In addition, the composition of intestinal flora is also crucial — probiotics (such as lactic acid bacteria) can promote the conversion of arginine into biologically active citrulline (the latter can be resynthesized into arginine in the kidneys), indirectly improving its utilization efficiency; while the overgrowth of pathogenic bacteria (such as Escherichia coli) will accelerate the decomposition of arginine into ammonia, reducing utilization.

IV. Impact of Physicochemical Properties and Formulation Technology

Stability and dosage form design: L-Arginine is a basic amino acid, which is prone to configuration changes in an acidic environment (such as in the stomach), affecting intestinal absorption. The use of enteric-coated preparations can avoid its degradation in the stomach, increasing bioavailability by 20%-40%. In addition, sustained-release preparations can maintain a more stable blood concentration by controlling the release rate of arginine and reducing the first-pass effect of the liver, which is especially suitable for scenarios requiring long-term supplementation (such as adjuvant treatment of cardiovascular diseases).

Dose-effect relationship: At low doses (≤5g per day), arginine is mainly absorbed through active transport, and bioavailability increases with the dose; but at high doses (>10g per day), active transport reaches saturation, and absorption turns to passive diffusion, with efficiency dropping sharply. Moreover, the unabsorbed part ferments in the intestine to produce excessive ammonia, which may cause side effects such as bloating and diarrhea, thereby reducing effective utilization.

The bioavailability of L-Arginine is the result of the combined action of intake methods, body metabolism, dietary interactions, and formulation characteristics. In practical applications, it is necessary to adjust the intake method and dose according to specific needs (such as nutritional supplementation and disease treatment), while paying attention to dietary collocation and body state to maximize the exertion of its physiological functions.