IMPORTANCE OF ALPHA-LACTALBUMIN IN INFANT NUTRITION

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IMPORTANCE OF ALPHA-LACTALBUMIN IN INFANT NUTRITION By Dr Dan Alaro

Learning Objective Describe the roles of α-lactalbumin as an important nutrients for infants.

Protein Composition : Human milk The whey-to Casein ratio affects amino acid composition and thus affects protein quality Casein & Whey proteins constitutes the principal proteins in breast milk. Whey-to-casein ratio in breast milk is variable and ranges from 90:10 to 50:50 during the normal course of lactation. Kunz C, Lönnerdal B. Re-evaluation of the whey protein/casein ratio of human milk. Acta Paediatr. 1992;81:107-112.

Amino acid composition : Human milk

Growth & Protein requirement during infancy Protein quality is measured in terms of amino acid composition A high-quality protein is highly digestible and contains essential amino acids in amounts that closely meet human needs Committee on Nutrition, American Academy of Pediatrics. Pediatric Nutrition Handbook. Kleinman RE, ed. 5th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2004:55-97, 103-106,229-240, 271, 551-592. BREAST MILK IS BEST FOR BABIES

Protein Composition : Human milk Vs Cows Milk Bovine Milk Human Milk Serum Albumin 1 % Lysozyme2% Renner et al,1983, (in Modified form )

Role of Alpha-lactalbumin 1) Nutrition 2) Immunity & protection from pathogens 3) Absorption of micronutrients 4) Milk formation BREAST MILK IS BEST FOR BABIES

1) Nutritional Role of alpha-lactalbumin: Alpha-lactalbumin is particularly rich in tryptophan, lysine, and cystein. Tryptophan is a precursor of serotonin, a neurotransmitter that regulates response to stress, sleep- wake rhythm and other physiologic process. Cystein is a constituent of the tripeptide gluthathione and a precursor of taurine. - Renner E (1983) Milk & Diary Products in Human Nutrition (Friedrich Pustet Germany - Yogman mw, Zeisel SH, Roberts C Assessing effect of Serotonin precursors on newborn behaviors J.Psychiatric Res 1982 17 123-33 - Heine WE Klein PD Reads PJ; The Importance of α-lactalbumin in infant Nutrition. J. Nutrition, 1991: 121: 277-83 Lo CW Human milk:nutritional properties. Walker. WA Watkin JB.Ed Nutrition in Pediatrics. Hamilton, Canada, Decker 1996. 436-48 BREAST MILK IS BEST FOR BABIES

2) Immunity & Protection GLF peptide = Gly-Leu-Phe peptide Partial proteolysis GLF peptides GLF stimulates neutrophils GLF increases phagocytosis by macrophages Intact alpha-lactalbumin Other antibacterial peptides Other antibacterial peptides reduce populations of potentially pathogenic bacteria Pellegrini A et al. Isolation and identification of three bactericidal domains in the bovine alpha-lactalbumin molecule. Biochim Biophys Acta 1999; 1426(3): 439-448. BREAST MILK IS BEST FOR BABIES

3) Absorptive role of alpha-lactalbumin Intact alpha-lactalbumin probably has only a limited ability to bind micro-nutrients and improve their absorption through the intestinal wall. However, during digestion, smaller peptides with the capacity to form complexes with cations are formed. Increased zinc absorption from formulas enriched with cows milk alpha-lactalbumin has been shown in infant rhesus monkeys Lönnerdal B. Biological Effects of Novel Bovine Milk Fractions 2011; 2. Kelleher SL et al. Am J Clin Nutr 2003; 77(5): 1261-1268. BREAST MILK IS BEST FOR BABIES BREAST MILK IS BEST FOR BABIES

4) Milk formation Eric L Lien Am J Clin Nutr 2003;77:1555S-1558S WN AfME BREAST MILK IS BEST FOR BABIES

Summary 1) Nutrition 2) Immunity & protection from pathogens 3) Absorption of micronutrients 4) Milk formation BREAST MILK IS BEST FOR BABIES

QUESTIONS?

Other benefits of a- Lactalbumin in infant feeding Improved amino acid profile ( Protein Quality) Support optimal Growth and development Cognitive development is intimately related to overall growth and development of a child including brain growth & development.

Other benefits of a- Lactalbumin in infant feeding Improvement of GI events in infant feeding. Prebiotic Effect to support in support of immune response Alpha Lactalbumin enriched Davis A et al JPGN 2005

References 1 Lönnerdal B. Biological Effects of Novel Bovine Milk Fractions 2011; 2. Kelleher SL et al. Am J Clin Nutr 2003; 77(5): 1261-1268. 17. Kunz C, Lönnerdal B. Re-evaluation of the whey protein/casein ratio of human milk. Acta Paediatr. 1992;81:107-112. Lönnerdal B. Nutritional and physiologic significance of human milk proteins. Am J Clin Nutr. 2003;77:1537S-1543S. 2 Marshall K. Therapeutic applications of whey protein. Alt Med Rev. 2004;9:136-156. 3 Food and Nutrition Board, Institute of Medicine of the National Academies. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press; 2005:5-13, 35,167-170, 283, 457, 620, 621, 630. 4 Food and Nutrition Board, Institute of Medicine of the National Academies. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press; 2005:5-13, 35, 167-170, 283, 457, 620, 621, 630. 5 Committee on Nutrition, American Academy of Pediatrics. Pediatric, Nutrition Handbook. Kleinman RE, ed. 6th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:16, 32-33, 71, 332, 334,349, 353, 723, 1201. 6 Committee on Nutrition, American Academy of Pediatrics. Pediatric Nutrition Handbook. Kleinman RE, ed. 5th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2004:55-97, 103-106,229-240, 271, 551-592. 7 J.Nutri 121. 277-283 1991, 8 Renner E (1983) Milk & Diary Products in Human Nutrition (Friedrich Pustet Germany 9 Yogman mw, Zeisel SH, Roberts C Assessing effect of Serotonin precursors on newborn behaviors J.Psychiatric Res 1982 17 123-33 10 Heine WE Klein PD Reads PJ; The Importance of α-lactalbumin in infant Nutrition. J. Nutrition, 1991: 121: 277-83 11 Lo CW Human milk : Nutritional properties. Walker. WA Watkin JB.Ed Nutrition in Pediatrics. Hamilton, Canada, Decker 1996. 436-48 12 Lien EL Davies AM Euler Multicentre study group.2014 Growth and Safety in term infants fed reduced protein formula with added bovine alpha lactalbumin J. Pediatric.Gastroent. Nutr. 170-176 13 Koletzko B, Von kries Closa R Escribamo J. Scaghioni S Grovanini M et al 2009. Lower protein in infant formula associated with lower weight up to age 2ys, a randomised clinical trail AM J Clinical Nutri 89, 1836-18 45 14 Trabulsi J, et al. The effect of 2 different protein concentrations in term infant formula on growth. J Pediatr Gastroenterol Nutr. 2009;48(suppl 3):E78. Abstract PN1-12. WN AfME BREAST MILK IS BEST FOR BABIES

Effect of an α-lactalbumin-enriched feeds with lower protein on growth European Journal of Clinical Nutrition (2011) 65, 167-174) Trabulsi J 1, Capeding R, Lebumfacil J, Ramanujam K, Feng P, McSweeney S, Harris B, DeRusso P. Background Protein Concentration is lower in human milk (HM) than in Infant formula. The objective of this study was to evaluate the effect of alphalactalbumin enriched feeds with a lower protein concentration on infant growth, protein markers and biochemistries Methods Healthy term formula Non-breastfed infants (FF) 5-14 days old were randomized in this controlled, double blind trail to standard feed (SF: 14.1 g/l protein, 662kcal/l) or experimental feed (EF: 12.8g/l protein, 622 kcal /l) group (n=112) for 120 days; a HM reference group (n=112) was included. Results 1 0 Outcome: Mean weight gain (g/day) did not differ significantly between SF vs EF. (P=0.67) nor between EF vs HM (P=0.11), however weight gain (g/day) was significantly greater in the SF vs HM(P=0.04) At day 120, mean weight-for- age Z-score (WAZ) and weight for length Z-score (WLZ) did not significantly differ between SF vs EF nor EF vs HM: however the WAZ was significantly greater in SF vs HM (p=0.025) 2 0 Outcome: Mean concentrations of plasma essential amino acids were similar to or slightly higher than in BM-fed infants EF was able to supply all necessary essential amino acids at a lower protein level than standard formula14 References Primary outcome was weight gain (g/day) from D0 to D120. Secondary outcome included serum albumin, plasma amino acids insulin and incidence of study events. Anthropometric measures were expressed as Z-Scores using 2006 World Health Organization growth standards European Journal of Clinical Nutrition (2011), 65, 167 174 doi: 10.1038/ejcn.2010.236;published online 10 Nov 2010. Conclusion Alphalactalbunim enriched feeds containing 12.8 g/l protein was safe and supported age-appropriate growth: weigh gain with EF was intermediate between SF and HM groups and resulted in growth similar to breastfed infants in terms of weight gains(waz and WLZ Infants randomized to the lower protein feeds had growth outcome similar to HM-fed infants in terns if weight gain, WAZ, WLZ 17

Alpha-lactalbumin: Principal fraction of Whey protein Whey protein fractions, expressed as a percentage of total protein in human milk