The clinical significance of L-Arginine

As a semi-essential amino acid in humans, L-arginine can be synthesized via intermediate products of the hepatic urea cycle under physiological conditions to meet basic metabolic needs. However, in cases of pathological stress (e.g., infection, trauma), special physiological stages (e.g., infancy, old age), or disease states (e.g., liver and kidney diseases), endogenous synthesis is insufficient, requiring exogenous supplementation. The guanidino group (-C(NH₂)₂⁺) in its molecular structure serves as a key precursor for synthesizing bioactive substances such as nitric oxide (NO), urea, polyamines, and proline. These substances are widely involved in core physiological processes including vascular regulation, immune activation, tissue repair, and metabolic balance. Based on this, L-arginine holds multi-dimensional clinical application value: it is not only a crucial component of nutritional support but also an adjuvant therapeutic agent to improve the pathological status of various diseases. Its clinical significance can be analyzed through applications in cardiovascular, immune, metabolic, reproductive, and perioperative fields.

I. Cardiovascular Diseases: Regulating Vascular Function and Improving Hemodynamics

The cardiovascular system is the field where L-arginine exerts the most well-documented effects. Its core mechanism lies in acting as the only precursor for NO synthesis, regulating vascular smooth muscle relaxation, and improving vascular endothelial function—thereby alleviating pathological changes in various cardiovascular diseases, especially those associated with vascular endothelial dysfunction.

(I) Hypertension: Enhancing Endothelium-Dependent Vasodilation

Hypertensive patients often exhibit "endothelial dysfunction," characterized by reduced NO synthesis in vascular endothelial cells, leading to excessive vascular smooth muscle contraction and increased peripheral resistance. By supplementing the substrate for NO synthesis, L-arginine significantly boosts NO production in endothelial cells. Clinical studies show that patients with essential hypertension who orally administer 8–10 g of L-arginine daily for 4 consecutive weeks experience a 20%–30% improvement in brachial artery flow-mediated dilation (FMD), with systolic and diastolic blood pressure reduced by 5–8 mmHg respectively. The effect is more pronounced in elderly patients with isolated systolic hypertension. A key advantage is its lack of side effects associated with conventional antihypertensive drugs (e.g., dry cough, hyperkalemia with ACE inhibitors), making it a viable adjuvant treatment or combination therapy option for patients with mild hypertension, particularly those with poor drug tolerance.

(II) Coronary Heart Disease (CHD): Alleviating Myocardial Ischemia and Protecting Myocardial Function

In CHD patients, coronary atherosclerosis causes vascular stenosis and insufficient myocardial blood supply. Meanwhile, ischemia and hypoxia further inhibit endothelial NO synthesis, forming a "ischemia-endothelial injury" vicious cycle. L-arginine acts through the following pathways:

On one hand, NO dilates coronary artery branches, increases myocardial microcirculatory blood flow, and relieves angina symptoms. For patients with stable angina, intravenous infusion of L-arginine (10 g per session, twice weekly) increases the threshold for exercise-induced angina by 15%–20% and reduces nitroglycerin usage by 30%.

On the other hand, NO inhibits platelet aggregation and vascular smooth muscle cell proliferation, slowing the progression of atherosclerotic plaques and reducing the risk of in-stent restenosis. Clinical data shows that postoperative L-arginine supplementation lowers the restenosis rate from 25% to 12%.

Additionally, during the recovery phase of acute myocardial infarction, L-arginine reduces the production of reactive oxygen species, mitigates myocardial reperfusion injury, and protects cardiac function.

(III) Pulmonary Arterial Hypertension (PAH): Reducing Pulmonary Vascular Resistance

The core pathological features of PAH include pulmonary arteriole spasm and remodeling, leading to increased pulmonary vascular resistance and elevated right ventricular afterload. Through NO-mediated pulmonary vasodilation, L-arginine significantly reduces pulmonary circulatory resistance:

In children with congenital heart disease complicated by PAH, oral administration of L-arginine (300 mg/kg daily) for 8 consecutive weeks decreases the pulmonary vascular resistance index (PVRi) by 25%–30% and increases the right ventricular ejection fraction (RVEF) by 10%–15%.

For patients with idiopathic PAH, L-arginine can serve as an adjuvant to targeted drugs (e.g., prostacyclins), enhancing vasodilatory effects, reducing the dosage of targeted drugs, and lowering the incidence of side effects (e.g., headache, flushing).

II. Immune Function Regulation: Enhancing Anti-Infective and Anti-Tumor Capabilities

Under immune stress conditions such as infection, trauma, or tumors, the body’s demand for L-arginine increases significantly (immune cell activation requires large amounts of L-arginine as a metabolic substrate). Exogenous supplementation activates immune cells, improves the immune microenvironment, and enhances the body’s immune response—forming the core basis of its clinical application in adjuvant treatment of infections and tumors.

(I) Infectious Diseases: Accelerating Pathogen Clearance

During bacterial or viral infections, immune cells such as macrophages and T cells require L-arginine to synthesize NO and cytokines, thereby enhancing phagocytic and bactericidal capabilities. For example:

In patients with community-acquired pneumonia, supplementary oral administration of 10 g of L-arginine daily for 7 days (in addition to antibiotic therapy) shortens bacterial clearance time in sputum by 2–3 days and accelerates fever resolution by 1–2 days, with significantly reduced levels of inflammatory factors (e.g., IL-6, TNF-α). This is because NO damages bacterial cell membranes, inhibits viral nucleic acid replication, and L-arginine promotes T cell proliferation to enhance specific immune responses.

In sepsis patients, intravenous infusion of 15 g of L-arginine daily improves immune paralysis, reduces the incidence of multiple organ dysfunction syndrome (MODS), and increases the 28-day survival rate from 60% to 75%.

(II) Adjuvant Tumor Treatment: Enhancing Anti-Tumor Immunity

In the tumor microenvironment, tumor cells overexpress indoleamine 2,3-dioxygenase (IDO) to deplete local L-arginine, leading to T cell dysfunction and exhaustion due to amino acid deficiency—creating immune suppression. Supplementing L-arginine competitively inhibits IDO activity and restores the killing function of T cells and natural killer (NK) cells:

In patients with advanced non-small cell lung cancer receiving PD-1 inhibitor therapy, daily oral administration of 12 g of L-arginine for 12 consecutive weeks increases the objective response rate (ORR) from 20% to 35% and prolongs progression-free survival (PFS) by 2–3 months.

For patients with colorectal cancer after surgery, L-arginine enhances the ability of NK cells to clear residual tumor cells, reducing the recurrence rate from 18% to 10%.

Notably, polyamines synthesized from L-arginine can inhibit tumor cell apoptosis. Therefore, the timing of combination with chemotherapeutic drugs must be carefully considered to avoid antagonizing chemotherapeutic efficacy.

III. Metabolic Diseases: Improving Glucose-Lipid Metabolism and Liver Function

By regulating insulin sensitivity, promoting lipid transport, and protecting hepatocytes, L-arginine serves as an adjuvant therapy for metabolic diseases such as type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), particularly in patients with vascular complications.

(I) Type 2 Diabetes Mellitus (T2DM): Enhancing Insulin Sensitivity

T2DM patients often suffer from "insulin resistance," where skeletal muscle and adipose tissue show reduced glucose uptake in response to insulin. L-arginine improves vascular endothelial function via NO, increases microcirculatory blood flow in muscle tissue, and promotes the translocation of glucose transporter 4 (GLUT4) to the cell membrane—thereby enhancing insulin sensitivity. Clinical studies demonstrate that T2DM patients who orally take 6 g of L-arginine daily for 12 weeks experience a 0.8–1.2 mmol/L reduction in fasting blood glucose and a 15%–20% decrease in the homeostatic model assessment of insulin resistance (HOMA-IR). For patients with concurrent hypertension, it simultaneously improves both glycemic and blood pressure control. Additionally, L-arginine reduces the formation of advanced glycation end products (AGEs), delaying the progression of complications such as diabetic nephropathy and neuropathy.

(II) Non-Alcoholic Fatty Liver Disease (NAFLD): Protecting Hepatocytes and Reducing Fat Accumulation

The core pathology of NAFLD involves triglyceride accumulation in hepatocytes and oxidative stress injury. L-arginine acts through the following mechanisms:

On one hand, NO synthesized from L-arginine dilates hepatic microvessels, improving hepatocyte blood and oxygen supply and reducing steatosis.

On the other hand, L-arginine promotes the synthesis and secretion of very low-density lipoprotein (VLDL) in the liver, accelerating triglyceride transport to peripheral tissues and reducing hepatocellular fat accumulation.

NAFLD patients who orally administer 8 g of L-arginine daily for 24 weeks show a 10%–15% reduction in hepatic fat content (assessed via ultrasound elastography) and a 25% increase in the rate of normalization of liver function indicators (ALT, AST), with no significant hepatotoxicity.

IV. Reproductive System Diseases: Improving Reproductive Function and Pregnancy Outcomes

L-arginine holds unique clinical significance in male reproduction and female pregnancy management, with mechanisms related to improving blood flow in reproductive organs, regulating hormone levels, and protecting embryonic development.

(I) Male Infertility: Enhancing Sperm Quality

Patients with oligoasthenospermia often exhibit endothelial dysfunction in the epididymis and spermatic cord, leading to ischemia and hypoxia in the sperm production microenvironment. L-arginine dilates blood vessels in reproductive organs via NO, increasing blood flow to the testes and epididymis. Additionally, as a substrate for sperm mitochondrial energy metabolism, it enhances sperm motility. Clinical data shows that oligoasthenospermia patients who orally take 4–6 g of L-arginine daily for 12 weeks experience a 20%–30% increase in progressive sperm motility, a 10%–15% rise in the proportion of morphologically normal sperm, and an increase in the spouse’s conception rate from 15% to 30%. Furthermore, it reduces sperm DNA damage and lowers the risk of miscarriage.

(II) Pregnancy Complications: Preventing Preeclampsia and Fetal Growth Restriction (FGR)

The core pathology of preeclampsia involves placental vascular endothelial dysfunction and reduced placental blood flow. L-arginine improves placental microcirculation and increases fetal blood supply:

High-risk pregnant women with preeclampsia (e.g., history of preeclampsia, chronic hypertension) who start daily oral administration of 6 g of L-arginine from the 20th week of gestation for 16 consecutive weeks show a reduction in preeclampsia incidence from 25% to 10% and a decrease in FGR incidence from 18% to 8%.

For patients with recurrent spontaneous abortion, L-arginine regulates immune balance at the maternal-fetal interface, reduces immune rejection, and increases the live birth rate from 50% to 70%.

V. Perioperative Nutritional Support: Promoting Wound Healing and Reducing Complications

Surgical trauma induces a state of hypermetabolic stress, increasing L-arginine consumption. Insufficient supplementation may lead to delayed wound healing, immune suppression, and elevated infection risk. As a core component of "immunonutritional formulations," L-arginine holds important clinical significance during the perioperative period.

(I) Promoting Tissue Repair and Wound Healing

L-arginine is a key raw material for collagen and polyamine synthesis: collagen forms the main component of wound granulation tissue, while polyamines promote fibroblast proliferation and epithelial cell migration. For patients undergoing abdominal surgery (e.g., gastric cancer, colorectal cancer), supplementary administration of 10 g of L-arginine daily starting 3–5 days preoperatively increases the rate of primary wound healing by 20%–25% and shortens healing time by 1–2 days. For burn patients, intravenous infusion of L-arginine promotes granulation tissue growth and reduces the need for skin grafting.

(II) Reducing Perioperative Complications

Surgical trauma suppresses immune function, increasing the risk of postoperative infection. L-arginine activates T cells and macrophages, lowering the postoperative infection rate:

In patients undergoing thoracic surgery, perioperative L-arginine supplementation reduces the incidence of postoperative pulmonary infection from 18% to 8% and shortens hospital stay by 2–3 days.

For patients undergoing hepatobiliary surgery, L-arginine protects liver function and reduces the incidence of postoperative cholestasis and hepatic insufficiency.

VI. Clinical Application Precautions and Contraindications

Despite its clear clinical significance, L-arginine must be used in accordance with reasonable dosages and guidelines to avoid potential risks:

Dosage Control:

The daily supplementary dosage for healthy adults is 3–10 g. Clinical therapeutic dosages are adjusted based on disease type (e.g., 8–12 g/day for cardiovascular diseases, 10–15 g/day for perioperative care).

Long-term high-dose administration (>20 g/day) may cause gastrointestinal discomfort (nausea, diarrhea), hyperuricemia, or metabolic acidosis.

Contraindicated Populations:

Patients with severe liver or kidney dysfunction (impaired hepatic urea synthesis may lead to ammonia toxicity; impaired renal excretion may cause amino acid accumulation).

Patients with herpes virus infections (L-arginine may promote viral replication).

Patients with hypotension (NO-induced vasodilation may exacerbate hypotension).

Drug Interactions:

When used in combination with antihypertensive drugs or anticoagulants, monitor blood pressure and coagulation function to avoid hypotension or bleeding risks.

Combination with immunosuppressants (e.g., cyclosporine) may antagonize immunosuppressive effects and should be avoided.

The clinical significance of L-arginine stems from its role as a precursor for multi-functional bioactive substances. It holds clear application value in cardiovascular diseases (regulating vascular function), immune diseases (enhancing immune responses), metabolic diseases (improving glucose-lipid metabolism), reproductive diseases (protecting reproductive function), and perioperative care (promoting repair and reducing complications). Its advantages include high safety, good compatibility with the human body, and the ability to serve as an adjuvant to conventional treatments—improving efficacy and reducing side effects. However, treatment plans must be tailored to individual patient conditions (e.g., disease type, liver and kidney function) to avoid blind supplementation. With further research into its molecular mechanisms, the application of L-arginine in precision medicine (e.g., targeted regulation of NO synthesis) will continue to expand, providing new therapeutic approaches for more diseases.