The safety of L-Arginine as a food additive

As an alkaline amino acid naturally present in proteins, L-arginine (L-Arg) is also a semi-essential amino acid for humans (essential for infants and young children, endogenously synthesizable by adults but with increased demand under specific physiological conditions). It is widely used in the field of food additives, primarily functioning as a nutritional fortifier, food flavor improver, and processing property regulator. Its safety assessment relies on toxicological data from authoritative institutions, population exposure levels, and adaptability in special populations, while dosage optimization must consider different application scenarios, physiological needs of populations, and potential risk thresholds—ultimately achieving a balance between "efficacy and safety."

I. Safety Assessment of L-Arginine as a Food Additive

The safety assessment of L-arginine involves three aspects: basic toxicological data, safety certifications from authoritative institutions, and potential risks with contraindicated populations. The core logic is to verify its safety boundaries under regular and high-dose conditions through an "animal experiment → population observation → special case screening" framework.

1. Toxicological Basis: No Significant Acute or Long-Term Toxicity

Acute toxicity: L-arginine exhibits extremely low acute oral toxicity. Animal experiments (on rats and mice) show that its median lethal dose (LD₅₀) is far higher than the dosage used in conventional food additives: the oral LD₅₀ in rats exceeds 2000 mg/kg body weight, and some studies have even failed to identify a clear lethal dose (i.e., "no observed adverse effect level," NOAEL). This aligns with L-arginine’s nature as an endogenous substance in the human body—humans typically ingest 5–10 g of natural L-arginine daily through diet (e.g., meat, fish, dairy products, nuts), while the additional amount from food additives is usually 0.1%–2% (by food weight), well below the acute toxicity threshold and unlikely to cause acute poisoning.

Long-term and genotoxicity: Multiple subchronic (90-day) and chronic (over 12-month) animal experiments have found no cumulative organ damage caused by L-arginine. For example, rats given 1000 mg/kg body weight of L-arginine daily for a long period (5–10 times the conventional supplementary dose for adults) showed no histological abnormalities in major organs such as the liver, kidneys, and heart, nor did they exhibit inhibited weight gain or abnormal blood biochemical indicators (e.g., transaminases, creatinine). Genotoxicity tests (e.g., AMES test, chromosomal aberration test) also confirm that L-arginine does not induce gene mutations or chromosomal damage, ruling out potential carcinogenic or teratogenic risks.

2. Safety Certifications from Authoritative Institutions: Widely Recognized "Safe" Status

Mainstream international food safety institutions have explicitly recognized the safety of L-arginine as a food additive through systematic evaluations:

The Joint FAO/WHO Expert Committee on Food Additives (JECFA) classifies L-arginine as a food additive with "no specified acceptable daily intake (ADI)" (ADI value "not specified"). This classification is based on the fact that L-arginine is endogenously synthesizable by the human body, widely available in the diet, and its long-term safety has been fully verified by population exposure data—eliminating the need for a strict daily intake limit.

The U.S. Food and Drug Administration (FDA) designates L-arginine as a "Generally Recognized as Safe (GRAS)" substance, allowing it to be used as a nutritional fortifier and flavor regulator in baked goods, sports nutrition products, infant formula, and other food categories. Its application scope and limits comply with the Code of Federal Regulations (CFR) (e.g., the addition amount in infant formula generally does not exceed 5% of the total protein content).

The European Food Safety Authority (EFSA) also confirms the safety of L-arginine, stating that intake via food supplements (≤30 g/day) or ordinary food additives (≤10 g/day) poses no adverse effects on healthy adults. Only specific populations (e.g., patients with kidney disease) are advised to restrict intake.

These certifications indicate a global consensus on the safety of L-arginine for healthy populations at conventional food additive doses, with no need for concern about general health risks.

3. Potential Risks and Contraindicated Populations: Alert to "Dose Dependence" and "Individual Differences"

Despite its overall safety, L-arginine carries potential risks at high doses or in specific populations, which must be considered in safety assessments:

Short-term discomfort from high doses: Healthy adults who consume more than 15 g of L-arginine in a single dose (or over 30 g/day, typically via high-concentration supplements rather than ordinary food additives) may experience gastrointestinal irritation symptoms, such as nausea, diarrhea, bloating, or heartburn. These symptoms result from high-concentration amino acids stimulating the gastrointestinal mucosa and accelerating intestinal peristalsis. They usually resolve with dose reduction and pose no long-term harm.

Risks for populations with specific diseases:

Patients with kidney disease: The metabolism of L-arginine in the body produces urea (excreted via the kidneys). Patients with impaired renal function (e.g., chronic renal failure, uremia) have reduced urea excretion capacity. Excessive intake may increase renal burden and even induce hyperkalemia (some studies suggest high-dose L-arginine may affect potassium excretion), requiring strict restriction or medical supervision.

Patients with herpes virus infections (e.g., shingles, genital herpes): L-arginine is a substrate for herpes virus replication (e.g., HSV-1, HSV-2). High-dose intake may theoretically provide "nutrients" for the virus, accelerating replication or worsening symptoms. While ordinary food additive doses are insufficient to trigger this issue, infected individuals should avoid additional high-dose supplementation.

People with hypotension or taking antihypertensive drugs: L-arginine is a substrate for nitric oxide (NO) synthase and promotes NO production. As NO induces vasodilation, it may cause a slight decrease in blood pressure—usually negligible in healthy people. However, hypotensive patients or those taking antihypertensive drugs (e.g., calcium channel blockers, ACE inhibitors) may experience excessively low blood pressure (with symptoms like dizziness and fatigue) if they consume excessive L-arginine, requiring controlled intake.

Drug interactions: Beyond antihypertensives, L-arginine may interact slightly with anticoagulants (e.g., warfarin), insulin, or hypoglycemic drugs. For example, it may enhance the hypoglycemic effect of insulin, increasing the risk of hypoglycemia. Therefore, diabetic patients should monitor blood glucose changes when consuming fortified foods containing L-arginine.

II. Dosage Optimization of L-Arginine as a Food Additive

The core goal of dosage optimization is to determine the "minimum effective dose" based on food type, target population, and addition purpose—ensuring safety while avoiding resource waste or potential risks from over-addition. Specific scenarios are categorized as follows:

1. Fortification of Ordinary Foods: Low Doses for "Supplementing Dietary Gaps"

For ordinary foods such as bread, cereal, dairy products, and beverages, L-arginine is added to supplement amino acids that may be deficient in daily diets (e.g., low intake in vegetarians or the elderly due to dietary structure). Doses should align with daily physiological needs:

Healthy adults ingest approximately 5–10 g of natural L-arginine daily through diet. The additional amount from food additives is recommended to be 0.5–3 g/day (calculated based on the total daily consumption of the food), corresponding to a concentration of 0.1%–1% in food. For example, adding 0.1–1 g of L-arginine to 100 g of bread allows adults to consume an additional 0.3–3 g by eating 300 g of bread daily.

This dose can supplement dietary gaps (e.g., vegetarians may obtain an extra 1–2 g daily to meet recommended intake levels for healthy people) while remaining far below the threshold for gastrointestinal discomfort (15 g/dose) and avoiding renal burden. It is suitable for all healthy populations, including children (children’s doses can be calculated by body weight, approximately 1/2–2/3 of adult doses).

2. Foods for Special Medical Purposes: Precise Doses for "Meeting Pathological Needs"

For foods for special medical purposes—such as products for diabetics, low-protein foods for kidney patients, and nutritional foods for post-surgical recovery—L-arginine doses must be determined under the guidance of doctors or dietitians, based on the patient’s pathological status. The core principle is "needs-based supply and risk avoidance":

Foods for diabetics: L-arginine helps regulate blood glucose by promoting insulin secretion. The recommended dose is 1–2 g per serving (no more than 5 g/day) to avoid enhancing the effect of hypoglycemic drugs and causing hypoglycemia. It should also be paired with low-GI (glycemic index) ingredients to ensure stable blood glucose.

Foods for kidney patients: L-arginine intake must be strictly restricted, with an added dose usually not exceeding 0.5 g/day (or no additional addition). The patient’s total daily protein intake must be calculated (L-arginine should account for no more than 3% of total protein) to prevent increased renal metabolic burden. Specific doses are adjusted based on the patient’s creatinine clearance rate and blood urea nitrogen levels.

Foods for post-surgical recovery: Post-surgical patients require increased L-arginine intake to support tissue repair (it promotes collagen synthesis and enhances immunity). The recommended dose is 3–5 g/day, administered in divided doses via liquid foods (e.g., nutritional porridge, protein powder). This meets repair needs while avoiding gastrointestinal discomfort from single high doses.

3. Sports Nutrition Products: Moderately Higher Doses for "Enhancing Athletic Performance"

In sports nutrition products (e.g., sports drinks, energy bars, protein powders), L-arginine is added to improve muscle blood flow and alleviate exercise fatigue by promoting NO production. Doses can be higher than those in ordinary foods but must stay within safe limits:

For general fitness enthusiasts (exercising 3–5 times a week, 1–2 hours per session): The recommended dose is 5–10 g/day, taken in two portions (2.5–5 g each) 1 hour before exercise and 30 minutes after exercise. This enhances muscle oxygen supply efficiency without causing hypotension or gastrointestinal discomfort.

For professional athletes (during high-intensity training or competition): Doses can be increased to 10–15 g/day, but single doses should not exceed 10 g (to reduce gastrointestinal irritation risk). Contraindications (e.g., hypotension, herpes infections) must be ruled out, and post-exercise physical responses (e.g., dizziness, fatigue) should be monitored to ensure dose matches exercise intensity.

III. Conclusion: Core Balance Principles for Safety and Dosage

As a food additive, the core safety conclusion for L-arginine is: "completely safe for healthy populations at conventional doses, but requiring caution at high doses or in special populations." The key to dosage optimization lies in "scenario adaptation, individual differences, and risk control":

For ordinary foods, target "dietary supplementation" with doses of 0.5–3 g/day, with no safety concerns;

For foods for special medical purposes, target "pathological needs" with personalized doses to avoid worsening conditions;

For sports nutrition products, target "performance enhancement" with moderately higher doses (10–15 g/day), while avoiding contraindicated populations and high-dose discomfort.

Ultimately, both safety assessment and dosage optimization must center on the "physiological properties of natural amino acids." L-arginine is not an "exogenous chemical additive" but a natural component of human metabolism, with far lower risks than synthetic additives. By following the principle of "adding on demand and not exceeding safety thresholds," it can deliver nutritional benefits while ensuring food safety.