Safety assessment of L-leucine in infant formula food

As an essential amino acid for humans, L-leucine is safe when added to infant formula in accordance with standards. Its safety primarily depends on "reasonable intake and proportioning"; excessive intake or imbalanced ratios may cause metabolic burdens. The specific assessment is as follows:

I. Core Safety Basis: Physiological Functions and Metabolic Characteristics of Essential Amino Acids

Physiological Necessity: L-leucine is a branched-chain amino acid (BCAA) essential for infant growth and development. It participates in protein synthesis, energy metabolism, and muscle tissue construction, and plays a crucial role in brain development and immune function improvement. Infants cannot synthesize it independently and must obtain it from external sources such as formula foods, making it an indispensable nutrient in formula.

Metabolic Safety: L-leucine is mainly metabolized in skeletal muscles. Its metabolites can participate in the tricarboxylic acid cycle for energy production or be converted into ketone bodies and fatty acids, ultimately excreted as non-toxic products without accumulation in the body. Its metabolic pathway is mature; under normal intake, it does not impose additional burdens on the liver or kidneys. Safety is further enhanced when metabolized synergistically with other BCAAs (isoleucine and valine).

II. Safe Intake Range and Formula Food Standard Requirements

International Safety Standards: The Food and Agriculture Organization/World Health Organization (FAO/WHO) recommends a daily L-leucine intake of 160–200 mg/kg body weight for infants aged 0–6 months and 140–180 mg/kg body weight for toddlers aged 7–12 months. The European Food Safety Authority (EFSA) and the U.S. Food and Drug Administration (FDA) have similar recommendations, emphasizing "proportional intake with other BCAAs" (leucine:isoleucine:valine ≈ 2:1:1).

China’s Formula Food Standards: According to National Food Safety Standard for Infant Formula (GB 10765-2021), L-leucine content in infant formula must meet "100–350 mg per 100 kcal of energy," with total BCAAs not exceeding 20% of total protein. For follow-up formula and toddler formula, the content must match protein levels to ensure balanced proportions, and excessive individual addition is prohibited.

III. Potential Risks and Control Boundaries

Risks of Excessive Intake:

Metabolic Burden: Infants’ metabolic systems are immature; excessive L-leucine intake (more than twice the recommended amount) increases metabolic pressure on skeletal muscles and the liver, potentially causing accumulation of intermediate metabolites (e.g., α-ketoisocaproic acid) and inducing discomfort such as nausea and vomiting.

Imbalanced Ratios: Excessive individual addition of L-leucine disrupts the balance with isoleucine and valine, potentially competitively inhibiting absorption of other amino acids (e.g., tryptophan, tyrosine), which may affect brain development and immune function in the long term.

Renal Load: Excess amino acids require renal excretion, which may increase filtration pressure on infants’ kidneys, especially risky for infants with underdeveloped renal function.

Precautions for Special Populations:

Premature infants and low-birth-weight infants: With weaker metabolic capacity, their L-leucine intake must be strictly controlled, following the principle of "individualized formulas" to avoid excess.

Infants with inherited metabolic diseases (e.g., maple syrup urine disease): Deficient in BCAAs metabolic enzymes, they require strict restriction of L-leucine intake and must use special formula under medical guidance.

IV. Key Measures to Ensure Safety in Formula Foods

Precise Control of Addition Amount: During formula design, L-leucine must be added in proportion to the infant’s age and total protein content in accordance with standards. Excessive individual addition is avoided, and balanced BCAAs ratios are ensured.

Raw Material Purity Control: High-purity (≥98%) food-grade L-leucine raw materials are used to avoid contamination by impurities (e.g., other amino acids, heavy metals) and reduce safety risks.

Clinical Validation Support: Before marketing, formula foods must undergo clinical feeding trials to verify the safety and tolerability of L-leucine and other nutrients, ensuring no adverse effects from long-term consumption by infants.

Standardized Labeling: Product labels must clearly display the nutrition facts table, including L-leucine content and BCAAs ratios, to facilitate consumers and medical staff in assessing suitability.

L-leucine is safe when added to infant formula in accordance with national standards. Its safety is based on "essentiality, metabolic maturity, and proportional balance." Core risks stem from "excessive intake" and "imbalanced ratios," which can be effectively mitigated by strictly following formula standards, controlling addition amounts, and ensuring raw material purity. Special infants (e.g., premature infants, those with metabolic diseases) must select formula under professional guidance to ensure safe nutrient intake.