lactoferrin and Malnutrition

Recent advances in perinatal and neonatal intensive care have resulted in significant improvements in the survival of preterm extremely low-birthweight (PELBW) infants; however, extrauterine growth restriction (EUGR) and undernutrition occur frequently during hospitalization and are associated with adverse outcomes, including bronchopulmonary dysplasia, sepsis, and neurodevelopmental impairment. Early optimal parenteral nutrition with adequate amino acids and lipids, especially long-chain polyunsaturated fatty acids, has been shown to decrease the incidence of EUGR, bronchopulmonary dysplasia, necrotizing enterocolitis, sepsis, and retinopathy of prematurity in animal models and clinical trials. In PELBW infants, breast milk and probiotics have been shown to reduce the incidence of necrotizing enterocolitis, and lactoferrin has been demonstrated to prevent late-onset sepsis. Thus, early administration of optimal postnatal parenteral and enteral nutrients can help prevent neurodevelopmental impairment caused by EUGR, necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity, and recent evidence indicates such treatment is feasible.

Topics: Animals; Child Development; Diet; Enterocolitis, Necrotizing; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Lactoferrin; Malnutrition; Milk, Human; Parenteral Nutrition; Probiotics

Colostrum and milk are rich in proteins and peptides which play a crucial role in innate immunity when transferred to the offspring and may accelerate maturation of the immune system in neonates. The immunotropic properties of these proteins prompted investigators research their potential application in prevention and therapy. Lactoferrin (LF) exhibits antibacterial, antifungal, antiviral, antiparasitice, and antitumoral activities. It is protective with regard to intestinal epithelium, promotes bone growth, and accelerates the recovery of immune system function in immunocompromised animals. LF was tried in the treatment of hepatitis C infection and the intestinal form of graft-versus-host disease (GvHD). A proline-rich polypeptide (PRP) demonstrated a variety of immunotropic functions, including the promotion of T-cell maturation and inhibition of autoimmune disorders. PRP, in the form of chewable tablets (Colostrinin) was recently found to improve or stabilize the health status of Alzheimer's disease patients. Casein and casein-derived peptides showed protective activities in enamel demineralization and as caries-preventing agents. The protein hydrolyzates were also protective in diabetic animals, reduced tumor growth, had antihypertensive activity and diminished colicky symptoms in infants. Glycomacropeptide (GMP), a peptide derived from kappa-casein, exhibited various antibacterial and antithrombotic activities. Alpha-lactalbumin (LA) demonstrated antiviral, antitumoral and anti-stress properties. LA-enriched diets were anxiolytic, lowered blood pressure in rats, prevented diarrhea, and led to a better weight gain in malnourished children. HAMLET, a complex of LA and oleic acid, was effective in patients with cutaneous papillomas. Lysozyme found application in infant formulas, the treatment of periodentitis, and the prevention of tooth decay. Milk enriched in lysozyme was used in feeding premature infants suffering from concomitant diseases. Interesting, antibacterial properties were exhibited by lactoperoxidase. Both lysozyme and lactoperoxidase required cooperative action with LF in combating bacteria. In conclusion, preparations derived from milk and colostrum are effective, easily bioaccessible, and safe, finding wide application in prevention and therapy for newborns and adults.

Topics: Adult; Alzheimer Disease; Animals; Anti-Infective Agents; Antineoplastic Agents; Autoimmune Diseases; Caseins; Child; Colostrum; Female; Humans; Infant; Infant, Newborn; Intercellular Signaling Peptides and Proteins; Lactoferrin; Lactoperoxidase; Malnutrition; Milk Proteins; Neoplasms; Peptides; Pregnancy; Tooth Diseases

Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life.. A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12-23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L).. Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02).. Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.

Topics: Child Development; Dietary Supplements; Double-Blind Method; Female; Growth Disorders; Humans; Infant; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Lactoferrin; Malawi; Male; Malnutrition; Muramidase; Prospective Studies; Sprue, Tropical

Chronic childhood malnutrition, as manifested by stunted linear growth, remains a persistent barrier to optimal child growth and societal development. Environmental enteric dysfunction (EED) is a significant underlying factor in the causal pathway to stunting, delayed cognitive development, and ultimately morbidity and mortality. Effective therapies against EED and stunting are lacking and further clinical trials are warranted to effectively identify and operationalize interventions.. A prospective randomized placebo-controlled parallel-group randomized controlled trial will be conducted to determine if a daily supplement of lactoferrin and lysozyme, two important proteins found in breast milk, can decrease the burden of EED and stunting in rural Malawian children aged 12-23 months old. The intervention and control groups will have a sample size of 86 subjects each. All field and laboratory researchers will be blinded to the assigned intervention group, as will the subjects and their caregivers. The percentage of ingested lactulose excreted in the urine (Δ%L) after 4 h will be used as the biomarker for EED and linear growth as the measure of chronic malnutrition (stunting). The primary outcomes of interest will be change in Δ%L from baseline to 8 weeks and to 16 weeks. Intention-to-treat analyses will be used.. A rigorous clinical trial design will be used to assess the biologically plausible use of lactoferrin and lysozyme as dietary supplements for children at high risk for EED. If proven effective, these safe proteins may serve to markedly reduce the burden of childhood malnutrition and improve survival.. Clinicaltrials.gov, NCT02925026 . Registered on 4 October 2016.

Topics: Age Factors; Body Height; Child Development; Clinical Protocols; Dietary Supplements; Female; Growth Disorders; Humans; Infant; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Intention to Treat Analysis; Lactoferrin; Malawi; Male; Malnutrition; Muramidase; Nutritional Status; Prospective Studies; Research Design; Sprue, Tropical; Time Factors; Treatment Outcome

Malnutrition remains a leading contributor to the morbidity and mortality of children under the age of five worldwide. However, the underlying mechanisms are not well understood necessitating an appropriate animal model to answer fundamental questions and conduct translational research into optimal interventions. One potential intervention is milk from livestock that more closely mimics human milk by increased levels of bioactive components that can promote a healthy intestinal epithelium. We tested the ability of cow milk and milk from transgenic cows expressing human lactoferrin at levels found in human milk (hLF milk) to mitigate the effects of malnutrition at the level of the intestine in a pig model of malnutrition. Weaned pigs (3 weeks old) were fed a protein and calorie restricted diet for five weeks, receiving cow, hLF or no milk supplementation daily from weeks 3-5. After three weeks, the restricted diet induced changes in growth, blood chemistry and intestinal structure including villous atrophy, increased ex vivo permeability and decreased expression of tight junction proteins. Addition of both cow and hLF milk to the diet increased growth rate and calcium and glucose levels while promoting growth of the intestinal epithelium. In the jejunum hLF milk restored intestinal morphology, reduced permeability and increased expression of anti-inflammatory IL-10. Overall, this pig model of malnutrition mimics salient aspects of the human condition and demonstrates that cow milk can stimulate the repair of damage to the intestinal epithelium caused by protein and calorie restriction with hLF milk improving this recovery to a greater extent.

Topics: Animals; Cattle; Disease Models, Animal; Humans; Interleukin-10; Intestinal Mucosa; Lactoferrin; Male; Malnutrition; Milk; Swine