Protein Digestion of Baby Foods: Study Approaches and Implications for Infant Health

Gan, Junai; Bornhorst, Gail M.; Henrick, Bethany M.; German, J. Bruce

doi:10.1002/mnfr.201700231

Cited by 72 publications

(45 citation statements)

References 120 publications

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“…Food acts as a buffer in the stomach and induces gastric acid secretion which impacts the dissolution of weakly acid and basic drugs. Infants have a higher postprandial gastric pH in comparison to adults and, like gastric emptying, the meal content is also a dependent factor [ 61 ]. Moreover, it is not uncommon for an infant or a child to receive an oral drug with a food or beverage (e.g., applesauce, yogurt, or fruit juice) to promote compliance.…”

Section: Predicting Food Effectsmentioning

confidence: 99%

Food Effects on Oral Drug Absorption: Application of Physiologically-Based Pharmacokinetic Modeling as a Predictive Tool

Cheng

Wong

2020

Pharmaceutics

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The bioavailability of an orally administered small molecule is often dictated by drug-specific physicochemical characteristics and is influenced by many biological processes. For example, in fed or fasted conditions, the transit time within the gastrointestinal tract can vary, confounding the ability to predict the oral absorption. As such, the effects of food on the pharmacokinetics of compounds in the various biopharmaceutics classification system (BCS) classes need to be assessed. The consumption of food leads to physiological changes, including fluctuations in the gastric and intestinal pH, a delay in gastric emptying, an increased bile secretion, and an increased splanchnic and hepatic blood flow. Despite the significant impact of a drug’s absorption and dissolution, food effects have not been fully studied and are often overlooked. Physiologically-based pharmacokinetic (PBPK) models can be used to mechanistically simulate a compound’s pharmacokinetics under fed or fasted conditions, while integrating drug properties such as solubility and permeability. This review discusses the PBPK models published in the literature predicting the food effects, the models’ strengths and shortcomings, as well as future steps to mitigate the current knowledge gap. We observed gaps in knowledge which limits the ability of PBPK models to predict the negative food effects and food effects in the pediatric population. Overall, the further development of PBPK models to predict food effects will provide a mechanistic basis to understand a drug’s behavior in fed and fasted conditions, and will help enable the drug development process.

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Section: Predicting Food Effectsmentioning

confidence: 99%

Food Effects on Oral Drug Absorption: Application of Physiologically-Based Pharmacokinetic Modeling as a Predictive Tool

Cheng

Wong

2020

Pharmaceutics

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“…While human milk directly supplies infants with FAAs, human milk proteins could also provide the infant with FAAs via proteolysis in the neonatal gastrointestinal tract. However, the contribution of proteolysis of human milk proteins to the FAA supply of infants might be relatively low, as (complete) proteolysis of these proteins in infants is shown to occur to a minimal extent (49)(50)(51)(52). Factors contributing to the limited proteolysis of human milk proteins are the relatively low output of pepsin and gastric enzymes observed in infants, the relatively high gastric postprandial pH which leaves proteases largely inactive, as well as the high degree of glycosylation of these proteins (50).…”

Section: Amino Acids In Human Milk: Protein-bound and Free Amino Acidsmentioning

confidence: 99%

Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections

et al. 2020

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“…One variable that exhibits considerable diversity across infants during digestion is pH . Human milk is neutral with a pH of around 7 .…”

Section: Introductionmentioning

confidence: 99%

Selective Proteolysis of α‐Lactalbumin by Endogenous Enzymes of Human Milk at Acidic pH

Gan

Zheng

Krishnakumar

et al. 2019

Molecular Nutrition Food Res

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Scope: The use of human milk products is increasing for high-risk infants. Human milk contains endogenous enzymes that comprise a dynamic proteolytic system, yet biological properties of these enzymes and their activities in response to variations including pH within infants are unclear. Human milk has a neutral pH around 7, while infant gastric pH varies from 2 to 6 depending on individual conditions. This study is designed to determine the specificity of enzyme-substrate interactions in human milk as a function of pH. Methods and results: Endogenous proteolysis is characterized by incubating freshly expressed human milk at physiologically relevant pH ranging from 2 to 7 without the addition of exogenous enzymes. Results show that the effects of pH on endogenous proteolysis in human milk are protein-specific. Further, specific interactions between cathepsin D and α-lactalbumin are confirmed. The endogenous enzyme cathepsin D in human milk cleaves α-lactalbumin as the milk pH shifts from 7 to 3. Conclusions: This study documents that selective proteolysis activated by pH shift is a mechanism for dynamic interactions between human milk and the infant. Controlled proteolysis can guide the use of human milk products based on individual circumstance.

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Protein Digestion of Baby Foods: Study Approaches and Implications for Infant Health

Cited by 72 publications

References 120 publications

Food Effects on Oral Drug Absorption: Application of Physiologically-Based Pharmacokinetic Modeling as a Predictive Tool

Food Effects on Oral Drug Absorption: Application of Physiologically-Based Pharmacokinetic Modeling as a Predictive Tool

Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections

Selective Proteolysis of α‐Lactalbumin by Endogenous Enzymes of Human Milk at Acidic pH

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