The application effect of L-Arginine in nutritional support for cancer patients

L-arginine is a semi-essential amino acid that plays a central role in various physiological processes such as immune regulation, nitrogen balance maintenance, protein synthesis, and angiogenesis. Cancer patients often suffer from malnutrition, immune deficiency, and muscle wasting due to tumor-related catabolism, radiotherapy/chemotherapy-induced damage, and anorexia. As a key component of immunonutrition, L-arginine is widely incorporated into nutritional support regimens for cancer patients. Its application value and efficacy should be comprehensively evaluated based on the patient’s disease course and treatment phase. The specific details are as follows:

I. Core Mechanisms of Action in Cancer Patients

Enhancing Host Immune Function

Cellular and humoral immunity are generally suppressed in cancer patients, and L-arginine serves as an essential substrate for the proliferation and activation of immune cells (T lymphocytes, NK cells, and macrophages):

As a precursor for nitric oxide (NO) synthesis, L-arginine is converted to NO by nitric oxide synthase (NOS). NO can enhance the cytotoxic activity of NK cells against tumor cells, promote macrophages to secrete cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2), and strengthen the anti-tumor immune response.

It facilitates the differentiation of T lymphocytes into cytotoxic effector T cells, ameliorates radiotherapy/chemotherapy-induced lymphopenia, and reverses the immunosuppressive state.

Improving Nitrogen Balance and Muscle Metabolism

The hypermetabolic nature of tumors and tissue damage caused by radiotherapy/chemotherapy can lead to negative nitrogen balance, accelerated muscle protein breakdown, and subsequent cachexia. L-arginine improves metabolic status through the following pathways:

It activates the mammalian target of rapamycin (mTOR) signaling pathway, promotes skeletal muscle protein synthesis, inhibits protein degradation, and alleviates cancer-associated muscle wasting.

As a precursor for glutamine synthesis, L-arginine supplementation can indirectly increase glutamine levels, which provide energy for rapidly proliferating immune cells and intestinal mucosal cells, thereby reducing muscle protein catabolism for energy supply.

It improves patient appetite, increases dietary intake, and synergistically corrects negative nitrogen balance.

Regulating the Tumor Microenvironment and Angiogenesis

The effect of L-arginine on the tumor microenvironment is bidirectional, which constitutes the core controversy of its application:

Anti-tumor effect: NO derived from immune cells can directly induce tumor cell apoptosis and inhibit tumor cell proliferation and invasion.

Potential pro-tumor risk: Tumor cells can overexpress arginase to consume local L-arginine for polyamine synthesis. Polyamines are key factors for tumor cell proliferation and angiogenesis, which may promote tumor growth. This bidirectional effect dictates that the application of L-arginine requires strict control of dosage and target population.

II. Application Scenarios in Nutritional Support for Cancer Patients

Perioperative Nutritional Support

For patients undergoing surgery for gastrointestinal cancer, breast cancer, lung cancer, etc., supplementation with L-arginine (often combined with glutamine, ω-3 fatty acids, etc.) for 7–10 days before surgery can significantly improve immune function, reduce the incidence of postoperative infectious complications (e.g., incision infection, pulmonary infection), and shorten the length of hospital stay.

Recommended dosage: 10–20 g/day, formulated into specialized immunonutritional preparations combined with other immunonutrients, administered via oral or enteral routes.

Contraindications: Patients with severe hepatic or renal insufficiency should use it with caution to avoid exacerbating metabolic burden.

Nutritional Intervention During Radiotherapy and Chemotherapy

Radiotherapy and chemotherapy can damage the gastrointestinal mucosa, suppress bone marrow hematopoietic function, and exacerbate immunosuppression and malnutrition in patients. L-arginine supplementation can:

Alleviate radiotherapy/chemotherapy-induced mucosal inflammation, promote intestinal mucosal repair, and reduce the incidence of diarrhea and mucositis.

Mitigate myelosuppression, increase white blood cell and lymphocyte counts, help patients tolerate the full course of radiotherapy/chemotherapy, and reduce the risk of treatment interruption.

Note: Dosage should be adjusted based on the patient’s blood routine, liver and kidney function during radiotherapy/chemotherapy; concurrent use with chemotherapeutic drugs with nephrotoxicity should be avoided.

Adjuvant Therapy for Cancer Cachexia

Cancer cachexia is characterized by progressive weight loss, muscle wasting, and anorexia, for which simple nutritional supplementation yields limited effects. The combination of L-arginine with ω-3 fatty acids, branched-chain amino acids, etc., can inhibit the release of inflammatory factors (e.g., IL-6, TNF-α) through synergistic effects, reduce muscle breakdown, delay cachexia progression, and improve patient quality of life.

III. Evidence-Based Medical Evidence and Controversies Regarding Application Efficacy

Established Clinical Evidence of BenefitsMultiple meta-analyses have shown that perioperative supplementation with immunonutritional preparations containing L-arginine can reduce the postoperative infection rate of cancer patients by 30%–40% and shorten the hospital stay by 2–3 days, which is particularly suitable for patients with gastrointestinal tumors.After supplementation with L-arginine, immunological parameters (CD4⁺/CD8⁺ ratio, NK cell activity) of patients undergoing radiotherapy/chemotherapy are significantly improved, treatment tolerance is enhanced, and quality of life scores (KPS score) are markedly elevated.

Core Controversies and Cautious Application ScenariosThe controversy over whether L-arginine promotes tumor growth is a key factor limiting its widespread use:

In vitro experiments and animal models have demonstrated that high-dose L-arginine may accelerate the growth of certain tumors (e.g., melanoma, colorectal cancer) by promoting polyamine synthesis or angiogenesis.

Clinical studies indicate that blind supplementation with L-arginine may pose potential risks for patients with advanced tumors or high tumor burden; whereas for patients with early-stage tumors or no residual lesions after surgery, the benefits outweigh the risks.

Therefore, the application of L-arginine requires individualized assessment and should be avoided as a routine nutritional support for patients with advanced or metastatic tumors.

IV. Application Principles and Precautions

Individualized Administration Regimen

Dosage: Recommended 10–30 g/day, divided into 2–3 doses to avoid single high-dose intake.

Route of administration: Enteral nutrition (oral or tube feeding) is preferred for synergistic absorption with other nutrients; if enteral nutrition is intolerable, small-dose supplementation via parenteral nutrition is acceptable.

Contraindicated and Cautious Populations

Contraindications: Patients with severe hepatic or renal failure (impaired excretion of arginine metabolites urea nitrogen and creatinine), patients with metabolic acidosis, and those allergic to L-arginine.

Cautious use: Patients with advanced tumors, those with bleeding tendency (NO may inhibit platelet aggregation), and patients receiving anti-angiogenic drug therapy.

Combined Nutritional Strategy

L-arginine has limited efficacy when used alone. It is recommended to combine it with other immunonutrients such as ω-3 polyunsaturated fatty acids, glutamine, and nucleotides to form an immunonutritional combination, which exerts multi-target effects to enhance efficacy while reducing the potential risks of single components.

The value of L-arginine in nutritional support for cancer patients is mainly reflected in perioperative immune enhancement, improved tolerance to radiotherapy/chemotherapy, and delayed cachexia, which is particularly suitable for patients with early to mid-stage tumors. Its application efficacy varies significantly among individuals, and the core is to avoid the “pro-tumor risk”. It should be comprehensively evaluated based on the patient’s tumor stage, treatment plan, and liver and kidney function, and used under the guidance of clinicians or clinical dietitians without blind supplementation.