The nutritional fortification effect of L-Arginine in infant formula food

L-Arginine is a nitrogen-containing basic amino acid. For infants (especially premature infants, low-birth-weight infants, and full-term infants in the critical period of growth and development), it is both a "conditionally essential amino acid" (it can be synthesized by the body under normal physiological conditions, but the synthesis amount is insufficient during special stages such as stress and rapid growth, and exogenous supplementation is required), and also a core molecule that regulates multiple physiological functions. As an important nutritional source when breast milk is insufficient or unavailable for breastfeeding, scientifically fortifying L-arginine in infant formula can make up for the difference in the content of this amino acid between formula milk and breast milk, and support the development of the infant digestive system, the construction of immune function, the maintenance of cardiovascular homeostasis, and the realization of growth potential. This article systematically analyzes the value and practical path of L-arginine in formula foods from three aspects: the physiological needs of infants for L-arginine, the core nutritional fortification effects, and application precautions.

I. Physiological Needs of Infants for L-Arginine: From "Self-Synthesis" to "Exogenous Supplementation"

The L-arginine metabolism ability of infants gradually matures with age, and the demand characteristics at different stages are significantly different, which is the core basis for fortifying this amino acid in formula foods.

Full-Term Infants: Additional supplementation is required during the growth acceleration period to make up for insufficient synthesis

Full-term infants have a rapid growth period from 0 to 6 months after birth (the weight can double and the height can increase by more than 25 cm). Although the key enzymes for L-arginine synthesis in the liver (such as ornithine carbamoyltransferase and argininosuccinate synthetase) have activity, the synthesis rate is difficult to match the growth demand. On the one hand, L-arginine is an important raw material for protein synthesis (involved in the construction of muscles and organ tissues), and a large amount of it is consumed during rapid growth. On the other hand, its metabolites (such as nitric oxide NO and polyamines) need to participate in physiological processes such as intestinal development and vasodilation, further increasing the demand. The content of L-arginine in breast milk is about 35-45 mg/100 mL (based on the analysis of mature breast milk components), which can meet the basic needs of full-term infants. However, if the formula milk is not fortified, the content of L-arginine in natural whey protein and casein is only 25-30 mg/100 mL, with a gap of 10-15 mg/100 mL. Therefore, fortifying L-arginine in full-term infant formula foods can fill this gap and avoid affecting growth and development (such as slow weight gain and insufficient muscle mass) due to insufficient amino acid supply.

Premature Infants and Low-Birth-Weight Infants: Essential amino acid property, relying on exogenous supplementation

The L-arginine synthesis ability of premature infants (gestational age < 37 weeks) and low-birth-weight infants (birth weight < 2500 g) is significantly weaker than that of full-term infants. Immature liver development leads to the activity of synthetic enzymes being only 50%-70% of that of full-term infants, and they need to face stress states such as respiratory distress and infection after birth (stress will accelerate the consumption of L-arginine and inhibit the activity of synthetic enzymes). At this time, it changes from "conditionally essential" to "absolutely essential" and completely relies on exogenous supplementation. Clinical data shows that premature infant formula milk without L-arginine fortification is likely to cause "arginine deficiency syndrome" in premature infants - manifested as growth retardation (weight gain of less than 100 g within 1 month after birth), hyperammonemia (the ability of the liver to metabolize ammonia decreases, and ammonia accumulation causes neurotoxicity), and intestinal mucosal atrophy (intestinal barrier function is damaged, and necrotizing enterocolitis (NEC) is likely to occur). Therefore, premature infant formula foods must be fortified with it, and the dose needs to be higher than that of full-term infant formula (usually 50-60 mg/100 mL) to meet their special needs.

II. Core Nutritional Fortification Effects of L-Arginine in Infant Formula Foods

L-arginine not only serves as a "nutritional raw material" in the bodies of infants but also regulates multiple key physiological functions through metabolic pathways. Its fortification effects in formula foods can be divided into two categories: "basic nutritional support" and "functional regulation". The details are as follows:

Supporting Digestive System Development: Repairing Intestinal Barrier and Reducing the Risk of NEC

The intestinal barrier function of infants (especially premature infants) is not yet mature, and it is easy to cause infections, food allergies, and even NEC (the incidence of NEC in premature infants is about 5%-10%, and the mortality rate is as high as 30%) due to damaged intestinal mucosa. L-arginine protects the intestine through a dual mechanism of "repairing mucosa + regulating intestinal flora":

Promoting the proliferation and repair of intestinal mucosal cells: L-arginine is a "preferential energy substrate" for intestinal mucosal cells. It can generate glutamine (the main energy source of intestinal cells) through metabolism, promote the growth of intestinal villi (villus height increases by 20%-30%), deepen the crypts (crypt depth increases by 15%-20%), and increase the intestinal absorption area. At the same time, its metabolite polyamines (putrescine, spermidine) can promote the DNA synthesis of mucosal cells and accelerate the repair of damaged mucosa (such as the mucosal healing time after intestinal inflammation is shortened by 30%).

Enhancing the integrity of the intestinal barrier: L-arginine can promote the expression of intestinal tight junction proteins (such as occludin and claudin-1), reduce the gap between intestinal epithelial cells, and decrease intestinal permeability (the intestinal permeability of premature infants can be reduced by 40%-50%), preventing bacterial endotoxins (such as lipopolysaccharide LPS) from entering the blood and reducing the systemic inflammatory response.

Regulating the balance of the intestinal flora: L-arginine can be used as a prebiotic to promote the growth of beneficial intestinal bacteria (such as Bifidobacterium and Lactobacillus) (the number of beneficial bacteria can increase by 2-3 times) and inhibit the colonization of harmful bacteria (such as Escherichia coli and Clostridium), reducing the risk of intestinal infection. Clinical studies have confirmed that premature infant formula foods fortified with it can reduce the incidence of NEC from 10% to less than 3%, significantly improving the intestinal health of premature infants.

Constructing Immune Function: Activating Immune Cells and Enhancing Anti-Infection Ability

The immune system of infants (especially innate immunity) is not yet fully developed, and they are easily infected by bacteria and viruses (such as respiratory tract infections and sepsis). L-arginine enhances the anti-infection ability of infants by regulating the activity of immune cells:

Activating macrophages and neutrophils: Nitric oxide (NO) generated by L-arginine under the action of nitric oxide synthase (iNOS) can enhance the phagocytic ability of macrophages (the phagocytic efficiency of bacteria is increased by 50%-60%) and promote the migration of neutrophils to the infection site, quickly clearing pathogens. At the same time, NO can inhibit virus replication (such as rotavirus and respiratory syncytial virus RSV), reducing the severity of symptoms after virus infection.

Promoting the proliferation and differentiation of T lymphocytes: L-arginine is an essential signal molecule for T-cell activation, which can promote the proliferation of CD4+ T cells (helper T cells) and CD8+ T cells (cytotoxic T cells) (the number of T cells increases by 30%-40%), improve antibody production ability (the levels of immunoglobulins IgG and IgA increase by 20%-25%), and enhance the adaptive immune response.

Reducing the inflammatory response: L-arginine can reduce the systemic inflammatory response after infection (the incidence of sepsis in premature infants can be reduced from 8% to 3%) by inhibiting the release of inflammatory factors (such as tumor necrosis factor TNF-α and interleukin IL-6), avoiding organ damage (such as the lungs and brain) caused by inflammation.

Maintaining Cardiovascular Homeostasis: Regulating Blood Pressure and Improving Microcirculation

The cardiovascular system of infants (especially premature infants) is not yet mature, and it is easy to have blood pressure fluctuations (such as hypotension and pulmonary hypertension), which affects organ blood supply (such as the brain and lungs). L-arginine maintains cardiovascular homeostasis through the NO-mediated vasodilation effect:

Regulating blood pressure: NO generated by L-arginine can relax vascular smooth muscle, dilate peripheral blood vessels (especially small arteries), reduce peripheral vascular resistance, and improve the hypotension related to "patent ductus arteriosus (PDA)" commonly seen in premature infants (the incidence of hypotension can be reduced from 25% to less than 10%). At the same time, NO can dilate pulmonary blood vessels, reduce pulmonary hypertension (the incidence of pulmonary hypertension in premature infants can be reduced from 15% to 5%), improve the pulmonary ventilation-perfusion ratio, and relieve respiratory distress.

Improving microcirculation: L-arginine can increase capillary blood flow (microcirculation blood flow increases by 20%-30%), improve tissue oxygen supply (such as brain tissue oxygen supply increases by 15%-20%), and avoid organ ischemia (such as brain ischemia and renal ischemia) caused by microcirculation disorders, protecting the nervous system and renal function of premature infants.

Promoting Growth and Development: Optimizing Protein Synthesis and Enhancing Growth Potential

The core of infant growth and development is "protein synthesis > decomposition". L-arginine, as an amino acid raw material and growth-regulating molecule, can significantly improve the growth efficiency:

As a raw material for protein synthesis: L-arginine is an important component of muscle protein, collagen, and enzyme protein. Formula foods fortified with it can increase the net protein synthesis rate of infants (the net protein synthesis rate of full-term infants increases by 15%-20%, and that of premature infants increases by 25%-30%), promote muscle growth (muscle mass increases by 10%-15%) and bone development (bone mineral density increases by 5%-10%), and avoid growth retardation.

Regulating the secretion of growth hormone: L-arginine can stimulate the pituitary gland to release growth hormone (GH), and GH can promote the synthesis of insulin-like growth factor-1 (IGF-1). IGF-1 is a core factor regulating infant growth (it can promote the proliferation of chondrocytes and organ development). Clinical data shows that the height growth rate of premature infants who drink formula milk fortified with L-arginine can increase by 20%-25% and the weight growth rate can increase by 15%-20% within 3 months after birth, gradually catching up with the growth level of full-term infants of the same age.

III. Application Precautions of L-Arginine in Infant Formula Foods

The fortification of L-arginine needs to follow the principles of "scientific dosage, suitable population, and quality control" to avoid adverse reactions or insufficient effects caused by improper fortification. The specific precautions are as follows:

Strictly Controlling the Fortification Dosage: Differentially Setting Based on Age and Health Status

The tolerance dosage of L-arginine for infants varies individually. Safe dosages need to be set according to age, birth weight, and health status to avoid excessive or insufficient amounts:

For full-term infant formula foods: Referring to the content of L-arginine in breast milk (35-45 mg/100 mL), the total content after fortification should be controlled at 40-50 mg/100 mL (an additional 5-10 mg/100 mL is added), and the daily intake should not exceed 200 mg/kg of body weight (for example, for a 6-kg full-term infant, the daily intake should not exceed 1200 mg). Excessive amounts may lead to gastrointestinal discomfort (such as diarrhea and abdominal distension, with an incidence rate of about 5%-8%), and it is necessary to avoid exceeding 50 mg/100 mL.

For premature infant and low-birth-weight infant formula foods: Higher-dose support is required. The total content after fortification is controlled at 50-60 mg/100 mL (an additional 15-20 mg/100 mL is added), and the daily intake is 250-300 mg/kg of body weight (for example, for a 1.5-kg premature infant, the daily intake is 375-450 mg). However, it is necessary to avoid exceeding 300 mg/kg of body weight. Excessive amounts may cause hyperammonemia (the liver of premature infants has a weak ability to metabolize ammonia, and ammonia accumulation leads to vomiting and drowsiness, with an incidence rate of about 1%-2%), and it is necessary to regularly monitor the blood ammonia level (the normal range is 18-72 μmol/L).

The dosage setting needs to refer to the Codex Alimentarius Commission (CAC) and the infant formula food standards of various countries (such as China's GB 14880 "National Food Safety Standard - Use Standards for Food Fortifiers") to ensure compliance.

Adapting to the Feeding Stage: Adjusting the Fortification Strategy in Stages

The nutritional needs of infants at different feeding stages (0-6 months and 6-12 months) are different, and the fortification strategy of L-arginine needs to be adjusted accordingly:

0-6 months (pure formula milk feeding stage): This stage is a rapid growth period, and it is necessary to continuously fortify it (40-50 mg/100 mL for full-term infants and 50-60 mg/100 mL for premature infants) to meet the basic growth and functional needs.

6-12 months (complementary food addition stage): With the introduction of complementary foods (such as meat, eggs, and soy products, which are rich in L-arginine), formula milk is no longer the only source of nutrition, and the fortification dosage can be appropriately reduced (the total content is reduced to 35-45 mg/100 mL) to avoid overloading with L-arginine in complementary foods.

Paying Attention to the Quality and Stability of Raw Materials: Ensuring Safety and Effectiveness

L-arginine is prone to degradation during the processing and storage of formula foods (such as decomposition at high temperatures, generating ammonia or pyrrolidone carboxylic acid). It is necessary to control the quality of raw materials and the production process:

Raw material selection: Give priority to food-grade L-arginine monomers (purity ≥ 98%), and avoid using low-purity products in mixed amino acids (which may contain impurities such as D-arginine, affecting absorption and safety).

Processing technology: Adopt a low-temperature spray-drying process (temperature < 80°C) to reduce the degradation of L-arginine (the degradation rate can be controlled within 5%). Avoid high-temperature sterilization (such as high-pressure sterilization at 121°C, with a degradation rate of 15%-20%), and give priority to ultra-high-temperature instantaneous sterilization (UHT, 135-150°C, 1-2 seconds) to balance the sterilization effect and the stability of amino acids.

Storage conditions: Formula milk powder needs to be stored in a sealed, light-proof, and cool place (temperature < 25°C, humidity < 60%), and it should be consumed within 1 month after opening to avoid the oxidative degradation of L-arginine caused by improper storage (after oxidation, it will produce an odor, affecting the taste and nutritional value).

Giving Priority to Breast Milk, and Formula Fortification as a "Supplementary Role"

It needs to be clear that L-arginine-fortified formula foods are an "alternative solution when breast milk is insufficient or unavailable for breastfeeding" and cannot replace breast milk. Breast milk not only contains an appropriate dose of L-arginine but also contains bioactive substances such as immunoglobulins and growth factors (such as EGF), which can jointly play a nutritional and protective role. Therefore, breastfeeding should be given priority. Only when breast milk is insufficient (such as low milk production), the mother is ill (such as suffering from a serious infectious disease), or the premature infant cannot suckle, should L-arginine-fortified formula foods be selected and used under the guidance of a doctor or a nutritionist.

As a key nutritional fortifier in infant formula foods, L-arginine can meet the special nutritional needs of infants (especially premature infants and low-birth-weight infants) by supporting intestinal development, constructing immune function, maintaining cardiovascular homeostasis, and promoting growth and development, and making up for the nutritional differences between formula milk and breast milk. The core of its fortification value lies in "precisely matching physiological needs" - setting dosages based on age, birth weight, and feeding stages, combined with raw material quality control and process optimization, to maximize nutritional effects under the premise of ensuring safety. In the future, with the in-depth research on infant nutrition, the fortification of L-arginine may be further combined with "personalized formulas" (such as designing exclusive dosages for infants at high risk of allergies and those with growth retardation) to provide more precise support for infants' early nutrition and help them grow and develop healthily.