Infant formulas are an alternative to replace or supplement human milk when breastfeeding is not possible. The knowledge of human milks bioactive compounds and their beneficial effects has attracted the interest of researchers in the field of infant nutrition, as well as researchers of technology and food sciences that seek to improve the nutritional characteristics of infant formulas. Several scientific studies evaluate the optimization of infant formula composition. The bioactive compound inclusion has been used to upgrade the quality and nutrition of infant formulas. In this context, the purpose of this systematic literature review is to assess the scientific evidence of bioactive compounds present in infant formulas (α-lactalbumin, lactoferrin, taurine, milk fat globule membrane, folates, polyamines, long-chain polyunsaturated fatty acids, prebiotics, and probiotics) and their effects on infant nutrition and health. Through previously determined criteria, studies published in the last fifteen years from five different databases were included to identify the advances in the optimization of infant formula composition. Over the last few years, there has been optimization of the infant formula composition, not only to increase the similarities in their content of macro and micronutrients but also to include novel bioactive ingredients with potential health benefits for infants. Although the infant food industry has advanced in the last years, there is no consensus on whether novel bioactive ingredients added to infant formulas have the same functional effects as the compounds found in human milk. Thus, further studies about the impact of bioactive compounds in infant nutrition are fundamental to infant health.

Infant formulas are manufactured products to meet specific nutritional requirements for infants. However, infant formulas can contain harmful substances, such as chemical contaminants and residues, normally due to possible contamination of the raw material or from the production chain. Some studies have demonstrated that veterinary drugs, pesticides, mycotoxins, heavy metals, packaging materials, within other chemicals are found in infant formulas from different sources of contamination. It is known that some of these substances can be hepatotoxic, carcinogenic, teratogenic, mutagenic, immunotoxic, contributing to antibiotic resistance, among other detrimental consequences for consumers’ health. The purpose of this review is to assess the scientific evidence concerning the occurrence, sources, and pathways of contamination, as well as the detrimental impacts on infant health due to the possible presence of chemical contaminants and residues in infant formulas. Moreover, strategies to reduce the risk of contamination of infant formulas are presented to ensure the highest standards of quality of infant formulas. The entire infant formula manufacturing process should be monitored and controlled to minimize the risk of contamination during processing, storage, and distribution, besides ensuring the use of raw materials with as low as acceptable levels of harmful substances in order to assure that the final product shall comply with the maximum levels and maximum residue limits, when established, for residues and contaminants in the final product.

Children are highly vulnerable to chemical exposure. Thus, metal and metalloid in infant formulas are a concern, although studies in this regard are still relatively scarce. Thus, the presence of aluminum, arsenic, cadmium, tin, mercury, lead, and uranium was investigated in infant formulas marketed in Brazil by inductively coupled plasma mass spectrometry, and the Target Hazard Quotients (THQ) and Target Cancer Risk (TCR) were calculated in to assess the potential risk of toxicity for children who consume these products continuously. Aluminum ranging from 0.432 ± 0.049 to 1.241 ± 0.113 mg·kg⁻¹, arsenic from 0.012 ± 0.009 to 0.034 ± 0.006 mg·kg⁻¹, and tin from 0.007 ± 0.003 to 0.095 ± 0.024 mg·kg⁻¹ were the major elements, while cadmium and uranium were present at the lowest concentrations. According to the THQ, arsenic contents in infant formulas showed a THQ > 1, indicating potential health risk concerns for newborns or children. Minimal carcinogenic risks were observed for the elements considered carcinogenic. Metabolic and nutritional interactions are also discussed. This study indicates the need to improve infant formula surveillance concerning contamination by potentially toxic and carcinogenic elements.

Phenolic compounds are recognized for their benefits against degenerative diseases. Clinical and nutritional applications are limited by their low solubility, stability, and bioavailability, compromising their efficacy. Natural macromolecules, such as lipids, polysaccharides, and proteins, employed as delivery systems can efficiently overcome these limitations. In this sense, proteins are attractive due to their biocompatibility and dynamic structure properties, functional adaptability and self‐assembly capabilities, offering stability, efficient encapsulation, and controlled release. This review explores the potential use of dairy proteins, caseins, and whey proteins, and, alternatively, nondairy proteins, gelatin, human serum albumin, maize zein, and soybean proteins, in building wall materials for the delivery of phenolic compounds. To optimize performance, aspects, such as protein–phenolic affinity and complex stability/activity, should be considered when designing particle nano‐architecture. Molecular interactions between protein–phenolic compound complexes are, thus, further discussed, as well as the effects of temperature and pH and strategies to stabilize and preserve nano‐architecture and retain phenolic compound activity. All proteins harbor one or more putative binding sites, shared or not, depending on the phenolic compound. Preservation techniques are still a case‐to‐case study, as no behavior patterns among different complexes are noted. Safety aspects necessary for the marketing of nanoproducts, such as characterization, toxicity assessments, and post‐market monitoring as defined by the European Food Safety Authority and the Food and Drug Administration, are discussed, evidencing the need for a unified regulation. This review broadens our understanding and opens new opportunities for the development of novel protein‐based nanocarriers to obtain more effective and stable products, enhancing phenolic compound delivery and health benefits.

Infant formulas, designed to provide similar nutritional composition and performance to human milk, are recommended when breastfeeding is not enough to provide for the nutritional needs of children under 12 months of age. In this context, the present study aimed to assess the protein quality and essential amino acid content of both starting (phase 1) and follow-up (phase 2) formulas from different manufacturers. The chemical amino acid score and protein digestibility corrected by the amino acid score were calculated. The determined protein contents in most formulas were above the maximum limit recommended by FAO and WHO guidelines and at odds with the protein contents declared in the label. All infant formulas contained lactoferrin (0.06 to 0.44 g·100 g⁻¹) and α-lactalbumin (0.02 to 1.34 g·100 g⁻¹) below recommended concentrations, whereas ĸ-casein (8.28 to 12.91 g·100 g⁻¹), α-casein (0.70 to 2.28 g·100 g⁻¹) and β-lactoglobulin (1.32 to 4.19 g·100 g⁻¹) were detected above recommended concentrations. Essential amino acid quantification indicated that threonine, leucine and phenylalanine were the most abundant amino acids found in the investigated infant formulas. In conclusion, infant formulas are still unconforming to nutritional breast milk quality and must be improved in order to follow current global health authority guidelines.

Pathophysiological conditions such as endothelial dysfunction and arterial stiffness, characterized by low nitric oxide bioavailability, deficient endothelium-dependent vasodilation and heart effort, predispose individuals to atherosclerotic lesions and cardiac events. Nitrate (NO₃⁻), L-arginine, L-citrulline and potassium (K⁺) can mitigate arterial dysfunction and stiffness by intensifying NO bioavailability. Dietary compounds such as L-arginine, L-citrulline, NO₃⁻ and K⁺ exert vasoactive effects as demonstrated in clinical interventions by noninvasive flow-mediated vasodilation (FMD) and pulse-wave velocity (PWV) prognostic techniques. Daily L-arginine intakes ranging from 4.5 to 21 g lead to increased FMD and reduced PWV responses. Isolated L-citrulline intake of at least 5.6 g has a better effect compared to watermelon extract, which is only effective on endothelial function when supplemented for longer than 6 weeks and contains at least 6 g of L-citrulline. NO₃⁻ supplementation employing beetroot at doses greater than 370 mg promotes hemodynamic effects through the NO₃⁻-NO2-/NO pathway, a well-documented effect. A potassium intake of 1.5 g/day can restore endothelial function and arterial mobility, where decreased vascular tone takes place via ATPase pump/hyperpolarization and natriuresis, leading to muscle relaxation and NO release. These dietary interventions, alone or synergically, can ameliorate endothelial dysfunction and should be considered as adjuvant therapies in cardiovascular diseases.