The promoting effect of L-Arginine on cardiovascular health

As a conditionally essential amino acid in humans, L-arginine can be catalyzed by nitric oxide synthase (NOS) to produce nitric oxide (NO)—a critical signaling molecule that plays a core regulatory role in cardiovascular functions such as vasodilation, anti-inflammation, and antithrombosis. Modern research indicates that exogenous supplementation of L-arginine provides multiple protections for cardiovascular health by improving vascular endothelial function, regulating blood pressure, and inhibiting the progression of atherosclerosis. It holds potential auxiliary intervention value, particularly for populations with hypertension, coronary heart disease (CHD), and peripheral vascular disease. This article analyzes the specific protective effects of L-arginine on the cardiovascular system from the perspective of its mechanism of action, clarifies applicable scenarios and precautions, and provides references for its scientific application.

I. Core Mechanism of Action: The NO-Centered Cardiovascular Regulatory Network

The protective effect of L-arginine on the cardiovascular system essentially relies on activating the normal physiological functions of vascular endothelial cells and repairing impaired cardiovascular regulatory mechanisms through the "L-arginine-NO pathway." The integrity of this pathway is key to maintaining vascular elasticity and stable blood flow, with specific mechanisms divided into three links:

(I) Producing Nitric Oxide (NO) to Relax Vascular Smooth Muscle

Vascular endothelial cells are the primary site for NO synthesis, and L-arginine is the only substrate for NO production: When L-arginine enters endothelial cells, it reacts with oxygen and nicotinamide adenine dinucleotide phosphate (NADPH) under the catalysis of NOS (classified into endothelial NOS [eNOS], neuronal NOS [nNOS], and inducible NOS [iNOS], with eNOS being the core enzyme for vascular homeostasis) to generate NO and citrulline. The produced NO rapidly diffuses into vascular smooth muscle cells, activating soluble guanylate cyclase (sGC) and increasing intracellular cyclic guanosine monophosphate (cGMP) levels. Elevated cGMP inhibits the influx of calcium ions (Ca²⁺) into smooth muscle cells, leading to smooth muscle relaxation and ultimately vasodilation.

This process is crucial for maintaining vascular elasticity: Under normal physiological conditions, NO is continuously released in small quantities to keep blood vessels moderately dilated and maintain stable peripheral vascular resistance. When L-arginine intake is insufficient or NOS activity is inhibited (e.g., due to oxidative stress or inflammation), NO production decreases, vascular relaxation function weakens, and this easily triggers increased blood pressure and hemodynamic disorders.

(II) Inhibiting Oxidative Stress and Inflammation to Protect Vascular Endothelium

Vascular endothelial injury is a common initiating link in cardiovascular diseases such as hypertension and atherosclerosis. L-arginine can delay the process of endothelial injury through dual "antioxidant + anti-inflammatory" effects:

1. Antioxidant Effect

L-arginine enhances the activity of antioxidant enzymes such as glutathione peroxidase and superoxide dismutase (SOD), scavenging excessive reactive oxygen species (ROS) (e.g., superoxide anions O₂⁻) in the body. ROS bind to NO to form peroxynitrite (ONOO⁻), inactivating NO. Supplementation with L-arginine reduces the consumption of NO by ROS, maintains the biological activity of NO, and prevents oxidative damage to endothelial cells caused by ROS (e.g., lipid peroxidation, DNA damage).

2. Anti-Inflammatory Effect

L-arginine inhibits the activation of nuclear factor κB (NF-κB)—a core pathway regulating the expression of inflammatory factors (e.g., tumor necrosis factor TNF-α, interleukin IL-6). When vascular endothelium is damaged, NF-κB is activated, triggering the release of large amounts of inflammatory factors and attracting leukocytes to adhere to the endothelial surface, exacerbating endothelial inflammation. Supplementation with L-arginine inhibits NF-κB activity via NO, reduces the secretion of inflammatory factors, lowers leukocyte adhesion rates, and alleviates vascular endothelial inflammation.

(III) Inhibiting Platelet Aggregation to Prevent Thrombosis

Thrombosis is a direct trigger for severe cardiovascular events such as acute myocardial infarction and cerebral infarction. L-arginine can inhibit platelet activation and aggregation through NO: Platelets have NO receptors on their surface; when NO binds to these receptors, it increases intracellular cGMP levels in platelets, inhibits the release of Ca²⁺ from platelets, and thereby prevents platelet adhesion to the vascular wall (avoiding binding to collagen and fibrinogen). It also inhibits platelet release of thromboxane A₂ (TXA₂), a potent platelet aggregator.

Clinical studies show that after healthy individuals supplement with L-arginine (8g daily for 2 weeks), platelet aggregation rates can decrease by 20%–30%. This mechanism is particularly effective for populations in a "hypercoagulable state" (e.g., diabetic patients, long-term bedridden individuals), reducing their risk of thrombosis.

II. Specific Protective Effects on Cardiovascular Health

Based on the regulatory role of the "L-arginine-NO pathway," L-arginine exhibits clear protective effects in improving blood pressure, delaying atherosclerosis, and protecting myocardial function, with differentiated application value in various cardiovascular disease scenarios:

(I) Auxiliary Blood Pressure Regulation and Improvement of Vascular Relaxation in Hypertensive Patients

One of the core pathological mechanisms of hypertension is "impaired vasodilation due to vascular endothelial dysfunction." L-arginine can address this defect by supplementing the substrate for NO production:

1. Effect on Essential Hypertension

Multiple randomized controlled trials have shown that patients with essential hypertension who supplement with L-arginine (6–10g daily) for 4–8 weeks experience a 5–10mmHg reduction in systolic blood pressure and a 3–5mmHg reduction in diastolic blood pressure. The mechanism involves L-arginine increasing NO levels, dilating peripheral arterioles, and reducing peripheral vascular resistance. This effect is particularly pronounced in "salt-sensitive hypertensive" patients, as L-arginine enhances vascular tolerance to sodium loading and reduces blood pressure fluctuations caused by a high-salt diet.

2. Potential Value for Gestational Hypertension

Gestational hypertension (preeclampsia) is often accompanied by endothelial dysfunction and insufficient NO production. Small-scale clinical studies indicate that supplementing L-arginine (4–6g daily) starting from the second trimester (20–24 weeks of gestation) can reduce the incidence of preeclampsia (from 15% to below 5%) while improving placental blood flow and reducing the risk of fetal growth restriction. Note: This must be done under medical guidance; self-supplementation is not recommended.

(II) Delaying Atherosclerosis Progression and Protecting Vascular Structure and Function

Atherosclerosis essentially involves "lipid deposition in vessel walls + inflammatory response + fibrous hyperplasia." L-arginine can inhibit its progression through multiple links:

1. Reducing Lipid Deposition

L-arginine inhibits the oxidative modification of low-density lipoprotein cholesterol (LDL-C) via NO. Oxidized LDL (ox-LDL) is a key initiator of atherosclerosis; it is phagocytosed by macrophages to form foam cells, which in turn trigger lipid deposition. Supplementing L-arginine reduces ox-LDL levels, decreases foam cell formation, and delays the early development of atherosclerotic plaques.

2. Stabilizing Atherosclerotic Plaques

Mature atherosclerotic plaques are classified as "stable" (thick fibrous cap, small lipid core) or "vulnerable" (thin fibrous cap, large lipid core, prone to rupture and thrombosis). L-arginine promotes vascular smooth muscle cells to synthesize collagen fibers via NO, thickening the plaque’s fibrous cap. It also inhibits the expression of inflammatory factors (e.g., IL-6, matrix metalloproteinase MMP-9) within the plaque, reducing the risk of plaque rupture.

Clinical observations show that CHD patients who supplement with L-arginine (8g daily) for 6 months in addition to conventional treatment (statins, aspirin) experience a 0.1–0.2mm reduction in carotid intima-media thickness (IMT, an early indicator of atherosclerosis) and a significant improvement in plaque stability.

(III) Improving Myocardial Blood Supply and Function, and Assisting in Relieving Myocardial Ischemia Symptoms

L-arginine protects ischemic myocardium by "dilating coronary arteries + improving myocardial cell energy metabolism":

1. Dilating Coronary Arteries to Increase Myocardial Blood Supply

Coronary arteries are the core vessels supplying blood to the myocardium. When coronary arteries are narrowed due to atherosclerosis, the myocardium is prone to ischemia and hypoxia (manifested as angina pectoris). NO produced by L-arginine can dilate coronary arteries and their branches, increasing coronary blood flow (clinical studies show that intravenous L-arginine infusion can increase coronary blood flow by 15%–20%). This relieves myocardial ischemia, reduces angina symptoms, and particularly decreases the frequency of nitroglycerin use in patients with "stable angina."

2. Protecting Myocardial Cells and Reducing Ischemia-Reperfusion Injury

After thrombolytic therapy or interventional treatment (e.g., stent implantation) for myocardial infarction, the reflow of blood to ischemic myocardium generates large amounts of ROS, causing "ischemia-reperfusion injury" and exacerbating myocardial cell necrosis. L-arginine inhibits ROS production via NO and promotes the repair of mitochondrial function in myocardial cells (mitochondria are the core site of energy metabolism). This reduces the size of myocardial infarction after reperfusion and improves cardiac function recovery (e.g., a 5%–10% increase in left ventricular ejection fraction [LVEF]).

(IV) Improving Peripheral Vascular Disease and Relieving Limb Ischemia Symptoms

Peripheral arterial disease (PAD) is a limb ischemia disorder caused by lower extremity atherosclerosis, characterized by intermittent claudication (pain and weakness in the lower limbs during walking), rest pain, and severe cases may lead to ulcers or gangrene. L-arginine improves limb blood circulation in PAD patients through the following mechanisms:

1. Dilating Lower Extremity Arteries to Increase Limb Blood Perfusion

NO produced by L-arginine dilates small arteries in the lower extremities, reduces lower limb vascular resistance, and improves blood supply to the feet and calves, relieving intermittent claudication symptoms. Studies show that PAD patients who supplement with L-arginine (12g daily) for 12 weeks experience a 30%–50% increase in pain-free walking distance and a 25% reduction in the incidence of rest pain.

2. Promoting Collateral Circulation Formation

When the main blood vessel is narrowed or occluded, the body can maintain tissue blood flow by forming "collateral vessels" (which replace the main vessel for blood supply). L-arginine promotes the expression of vascular endothelial growth factor (VEGF) via NO, stimulates the neovascularization of collateral vessels, and establishes a "compensatory blood flow channel" for ischemic limbs, reducing the risk of limb ischemia and necrosis.

III. Applicable Scenarios and Scientific Supplementation Recommendations

The protective effect of L-arginine on the cardiovascular system has clear target populations and supplementation standards. It should be applied rationally based on individual health conditions to avoid blind supplementation:

(I) Main Applicable Populations

Populations at high risk of cardiovascular disease: Individuals with prehypertension (systolic blood pressure 120–139mmHg), dyslipidemia (elevated LDL-C), diabetes (especially those at risk of vascular complications), and obesity (BMI > 28kg/m²). Supplementing L-arginine can improve endothelial function and prevent the development of cardiovascular disease.

Patients with confirmed cardiovascular disease: Individuals with stable hypertension (poor blood pressure control), stable angina, and PAD (intermittent claudication). Under medical guidance, L-arginine supplementation can serve as an auxiliary to conventional treatment, improving symptoms and prognosis.

Populations in special physiological stages: Pregnant women at high risk of gestational hypertension (with a family history of preeclampsia or previous preeclampsia). After evaluation by an obstetrician, short-term L-arginine supplementation can reduce the risk of developing the disease.

(II) Scientific Supplementation Regimens

1. Dosage

Daily health maintenance for healthy individuals: 3–5g daily, which can be obtained through diet (e.g., lean meat, fish, nuts, legumes; 100g of lean meat contains approximately 1–2g of L-arginine) or low-dose supplements. No additional high-dose supplementation is required.

Auxiliary intervention for cardiovascular disease: 6–12g daily, divided into 2–3 doses (e.g., 3g per dose, taken with meals to reduce gastrointestinal irritation). After 4–8 weeks of continuous supplementation, the dosage should be adjusted based on symptom improvement to avoid long-term high-dose intake.

Intravenous supplementation (requires medical monitoring): For patients with acute myocardial ischemia or severe PAD, intravenous L-arginine (5–10g per dose, dissolved in normal saline) can be administered in hospitals. Blood pressure and heart rate must be monitored by medical staff to avoid the risk of hypotension.

2. Supplementation Methods

Prioritize dietary intake: Foods rich in L-arginine include chicken breast, salmon, eggs, soybeans, walnuts, and pumpkin seeds. A balanced daily diet with reasonable combinations can meet basic needs.

Supplement selection: If additional supplementation is needed, choose "pure L-arginine preparations" or "L-arginine + citrulline composite preparations" (citrulline can be converted to L-arginine in the body, extending its duration of action). Avoid products with excessive additives (e.g., sucrose, flavorings).

3. Precautions

Avoid concurrent use with antihypertensive drugs and nitrates (e.g., nitroglycerin): Concurrent use of L-arginine with these drugs may cause excessive blood pressure reduction, leading to dizziness or syncope. If simultaneous use is necessary, an interval of more than 2 hours should be maintained, and blood pressure should be monitored.

Use with caution in patients with renal insufficiency: L-arginine metabolism in the body produces urea. Patients with renal insufficiency (e.g., serum creatinine > 178μmol/L) may experience increased renal burden after supplementation, so dosage adjustments must be made under medical guidance.

Be alert to gastrointestinal reactions: Some individuals may experience nausea, bloating, or diarrhea after taking L-arginine. It is recommended to start with a low dose (3g daily) and gradually increase the dosage; taking it with meals can reduce irritation.

Through the "L-arginine-NO pathway," L-arginine provides support for cardiovascular health through multiple dimensions, including vasodilation, anti-inflammation, antithrombosis, and endothelial protection. It demonstrates clear value in auxiliary blood pressure regulation, delaying atherosclerosis, and improving myocardial and peripheral vascular blood supply, making it particularly suitable for auxiliary intervention in populations at high risk of cardiovascular disease and patients with confirmed cardiovascular conditions.

Scientific application of L-arginine must follow the principles of "reasonable dosage and targeted supplementation." Priority should be given to dietary intake; supplements should be used under medical guidance when necessary, while avoiding the risk of concurrent use with antihypertensive drugs. It is important to note that L-arginine is not a "substitute for cardiovascular drugs." Patients with confirmed cardiovascular disease must continue standardized treatment (e.g., statins, aspirin, antihypertensive drugs) and should not discontinue prescription medications due to L-arginine supplementation. Only in this way can comprehensive protection of cardiovascular health be truly achieved.