Casein Peptides
OTHER NAME(S): C12, C12 Peptide, C12 Peption, Casein Decapeptide, Casein-derived Peptide, Casein-derived Lactotripeptides, Casein Peptide, Casein Hydrolysate, Casein Phosphopeptide, Casein Protein Hydrolysate, Casein Tripeptide, Cysteine Milk Peptide, eHC, eHCP, Extensively Hydrolyzed Casein Protein, Hydrolyzed Casein, Hypotensive Peptides, Isoleucine-Proline-Proline, Lactotripeptide, Lactotripeptides, Peptide C12, Peptides de Caseine, Peptides de Caséine, Peptides Hypotenseurs, Péptidos de la Caseína, Sour Milk Extract, Sour Milk Peptides, Tripeptide de Caséine, Valine-Proline-Proline, Casein peptides., C-12 Peptide, Casein Protein Extract, C-12, Sour Milk Extract, Casein Phosphopeptide, C12, Milk Protein Extract, Péptidos de Caseína, Peptides De Caséine
Overview
Casein protein makes up about 80% of the protein found in milk. When consumed, the body breaks casein down into smaller pieces called casein peptides.
Casein peptides can also be made in the lab and used in supplements. It's sometimes called "casein hydrolysate" or "hydrolyzed casein" on labels. Some casein peptides might have effects that lower blood pressure. They might also have antiallergy effects when used instead of cow's milk.
People use casein peptides for eczema, food allergies, and being prone to allergies and allergic reactions (atopic disease). They are also used for colic, diabetes, high blood pressure, neonatal jaundice, asthma, infant development, acne, stress, and many other conditions, but there is no good evidence to support most of these uses.
Don't confuse casein peptides with casein protein. These are not the same.
Uses
Likely Effective for
- Eczema (atopic dermatitis). Feeding infants formula containing casein peptides with or without breastmilk for up to 6 months reduces the chances of getting eczema.
- Prone to allergies and allergic reactions (atopic disease). Feeding infants formula containing casein peptides instead of cow's milk reduces the risk for allergies in infants with a family history of allergic conditions. But it's not clear if it benefits infants without a family history of allergic conditions.
- Food allergies. Some formulas containing casein peptides are safe and do not cause allergic reactions in children who have an allergic reaction to cow's milk. These formulas include Alimentum, Damira 2000, Frisolac Allergycare, and Nutramigen.
Possibly Effective for
- Excessive crying in infants (colic). Feeding infants with colic a formula containing casein peptides reduces crying short-term.
- Diabetes. Eating casein peptides with carbohydrates might improve insulin and glucose levels after a meal in people with type 2 diabetes. It's not clear if casein peptides reduce the risk for type 1 diabetes in infants.
- High blood pressure. Taking certain casein peptides, sometimes called lactotripeptides, seem to lower blood pressure by a small amount in people with high blood pressure.
- High levels of a chemical called bilirubin in the blood of newborns (neonatal jaundice). Feeding infants formula containing casein peptides instead of a formula containing whey protein or breastmilk seems to reduce the risk of jaundice in newborns.
Possibly Ineffective for
- Asthma. Feeding infants formula containing casein peptides, with or without breastmilk, doesn't reduce the risk of asthma in infants.
- Infant development. Feeding premature, low-birth weight, or healthy infants a formula containing casein peptides does not increase or decrease growth when compared with breast milk or other formulas.
There is interest in using casein peptides for a number of other purposes, but there isn't enough reliable information to say whether it might be helpful.
Side Effects
When taken by mouth: Casein peptides are likely safe when consumed appropriately. They're usually well-tolerated.
Precautions
When taken by mouth: Casein peptides are likely safe when consumed appropriately. They're usually well-tolerated.
Pregnancy and breast-feeding: There isn't enough reliable information to know if casein peptides are safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use.
Infants and children: Casein peptides are likely safe for children and infants when taken by mouth appropriately. Most infants receiving casein peptide-based formulas do not experience side effects.
Milk allergy: People with milk allergy are allergic to the proteins contained in milk. They may also be allergic to fragments of milk proteins, such as casein peptides. If you have a milk allergy, it's best to avoid taking casein peptides. There are some specific casein peptide formulas that can be safely given to infants with milk allergy. These formulas are: Alimentum, Damira 2000, Frisolac Allergycare, and Nutramigen.
Surgery: Casein peptides might affect blood pressure. This might interfere with blood pressure control during and after surgery. Stop taking casein peptides at least 2 weeks before a scheduled surgery.
Interactions
Minor Interaction
Be watchful with this combination
- Medications for high blood pressure (Antihypertensive drugs) interacts with Casein PeptidesCasein peptides might lower blood pressure. Taking casein peptides along with medications that lower blood pressure might cause blood pressure to go too low. Monitor your blood pressure closely.
Dosing
Casein peptides have most often been used by adults in doses up to 10.5 mg by mouth for 21-48 weeks. In infants and newborns, specific casein peptide formulas (Nutramigen or Progestimil, Mead Johnson) have been used for up to 18 months. Speak with a healthcare provider to find out what type of product and dose might be best for a specific condition.
References
- Townsend RR, McFadden CB, Ford V, Cadee JA. A randomized, double-blind, placebo-controlled trial of casein protein hydrolysate (C12 peptide) in human essential hypertension. Am J Hypertens 2004;17(11 Pt 1):1056-8.
- Park O, Swaisgood HE, Allen JC. Calcium binding of phosphopeptides derived from hydrolysis of alpha s-casein or beta-casein using immobilized trypsin. J Dairy Sci 1998;81:2850-7.
- Gill HS, Doull F, Rutherfurd KJ, Cross ML. Immunoregulatory peptides in bovine milk. Br J Nutr 2000;84:S111-7.
- Wal JM. Cow's milk proteins/allergens. Ann Allergy Asthma Immunol 2002;89:3-10.
- Tauzin J, Miclo L, Gaillard JL. Angiotensin-I-converting enzyme inhibitory peptides from tryptic hydrolysate of bovine alphaS2-casein. FEBS Lett 2002;531:369-74.
- Claustre J, Toumi F, Trompette A, et al. Effects of peptides derived from dietary proteins on mucus secretion in rat jejunum. Am J Physiol Gastrointest Liver Physiol 2002;283:G521-8.
- Nishi T, Hara H, Hira T, Tomita F. Dietary protein peptic hydrosylates stimulate cholecystokinin release via direct sensing by rat intestinal mucosal cells. Exp Biol Med (Maywood) 2001;226:1031-6.
- Wal JM. Structure and function of milk allergens. Allergy 2001;56:35-8.
- Yamamoto N. Antihypertensive peptides derived from foods. Biopoly 1997;43:129-34.
- Demling, R. H. and DeSanti, L. Effect of a hypocaloric diet, increased protein intake and resistance training on lean mass gains and fat mass loss in overweight police officers. Ann Nutr Metab 2000;44(1):21-29.
- Rzehak, P., Sausenthaler, S., Koletzko, S., Reinhardt, D., von, Berg A., Kramer, U., Berdel, D., Bollrath, C., Grubl, A., Bauer, C. P., Wichmann, H. E., and Heinrich, J. Long-term effects of hydrolyzed protein infant formulas on growth--extended follow-up to 10 y of age: results from the German Infant Nutritional Intervention (GINI) study. Am J Clin.Nutr 2011;94(6 Suppl):1803S-1807S.
- Verdijk LB, Jonkers RA, Gleeson BG, et al. Protein supplementation before and after exercise does not further augment skeletal muscle hypertrophy after resistance training in elderly men. Am J Clin Nutr 2009;89(2):608-16.
- Saunders MJ, Moore RW, Kies AK, et al. Carbohydrate and protein hydrolysate coingestions improvement of late-exercise time-trial performance. Int J Sport Nutr Exerc Metab 2009;19(2):136-49.
- Koopman R, Crombach N, Gijsen AP, et al. Ingestion of a protein hydrolysate is accompanied by an accelerated in vivo digestion and absorption rate when compared with its intact protein. Am J Clin Nutr 2009;90(1):106-15.
- Forsyth BW. Colic and the effect of changing formulas: a double-blind, multiple-crossover study. J Pediatr 1989;115(4):521-6.
- Jakobsson I, Lothe L, Ley D, Borschel MW. Effectiveness of casein hydrolysate feedings in infants with colic. Acta Paediatr 2000;89(1):18-21.
- Manders RJ, Hansen D, Zorenc AH, et al. Protein co-ingestion strongly increases postprandial insulin secretion in type 2 diabetes patients. J Med Food 2014;17(7):758-63.
- Knip M, Virtanen SM, Becker D, et al. Early feeding and risk of type 1 diabetes: Experiences from the Trial to Reduce Insulin-dependent diabetes mellitus in the Genetically at Risk (TRIGR). Am J Clin Nutr 2011;94(6 Suppl):1814S-1820S.
- Manders RJ, Wagenmakers AJ, Koopman R, et al. Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes. Am J Clin Nutr 2005;82(1):76-83.
- Manders RJ, Praet SF, Meex RC, et al. Protein hydrolysate/leucine co-ingestion reduces the prevalence of hyperglycemia in type 2 diabetic patients. Diabetes Care 2006;29(12):2721-2.
- Manders RJ, Koopman R, Sluijsmans WE, et al. Co-ingestion of a protein hydrolysate with or without additional leucine effectively reduces postprandial blood glucose excursions in type 2 diabetic men. J Nutr 2006;136(5):1294-9.
- Manders RJ, Praet SF, Vikstrom MH, et al. Protein hydrolysate co-ingestion does not modulate 24 h glycemic control in long-standing type 2 diabetes patients. Eur J Clin Nutr 2009;63(1):121-6.
- Geerts BF, van Dongen MG, Flameling B, et al. Hydrolyzed casein decreases posprandial glucose concentrations in T2DM patients irrespective of leucine content. J Diet Suppl 2011;8(3):280-92.
- Jonker JT, Wijngaarden MA, Kloek J, et al. Effects of low doses of casein hydrolysate on post-challenge glucose and insulin levels. Eur J Intern Med 2011;22(3):245-8.
- Pedrosa M, Pascual CY, Larco JI, Esteban MM. Palatability and hydrolysates and other substitution formulas for cow's milk-allergic children: a comparative study of taste, smell, and texture evaluated by healthy volunteers. J Investig Allergol Clin Immunol 2006;16(6):351-6.
- Field KL, Kimball BA, Mennella JA, et al. Avoidance of hydrolyzed casein by mice. Physiol Behav 2008;93(1-2):189-99.
- Roy CC, Darling P. Pitfalls in the design and manufacture of infant formulas. J Pediatr Gastroenterol Nutr 1983;2 Suppl 1:S282-92.
- Gourley GR, Kreamer B, Cohnen M, Kosorok MR. Neonatal jaundice and diet. Arch Pediatr Adolesc Med 1999;153(2):184-8.
- Gourley GR, Li Z, Kreamer BL, Kosorok MR. A controlled, randomized, double-blind trial of prophylaxis against jaundice among breastfed newborns. Pediatrics 2005;116(2):385-91.
- Rzehak P, Sausenthaler S, Koletzko S, et al. Short- and long-term effects of feeding hydrolyzed protein infant formulas on growth at = 6 y of age: Results from the German Infant Nutritional Intervention Study. Am J Clin Nutr 2009;89(6):1846-56.
- de Mattos AP, Ribeiro TC, Mendes PS, et al. Comparison of yogurt, soybean, casein, and amino acid-based diets in children with persistent diarrhea. Nutr Res 2009;29(7):462-9.
- Gourley GR, Kreamer B, Arend R. The effect of diet on feces and jaundice during the first 3 weeks of life. Gastroenterology 1992;103(2):660-7.
- Gourley GR, Kreamer BL, Cohnen M. Inhibition of beta-glucuronidase by casein hydrolysate formula. J Pediatr Gastroenterol 1997;25:267-72.
- Gourley GR, Arenda RA. beta-Glucuronidase and hyperbilirubinaemia in breast-fed and formula-fed babies. Lancet 1986;1:644-6.
- Mallet E, Henocq A. Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants. J Pediatr 1992;121(5 Pt 2):S95-100.
- Oldaeus G, Anjou K, Bjorksten B, et al. Extensively and partially hydrolysed infant formulas for allergy prophylaxis. Arch Dis Child 1997;77(1):4-10.
- Halken S, Hansen KS, Jacobsen HP, et al. Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study. Pediatr Allergy Immunol 2000;11(3):149-61.
- von Berg A, Koletzko S, Grubl A, et al. The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial. J Allergy Clin Immunol 2003;111(3):533-40.
- von Berg A, Koletzko S, Filipiak-Pittroff B, et al. Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study. J Allergy Clin Immunol 2007;119(3):718-25.
- von Berg A, Filipiak-Pittroff B, Kramer U, et al. Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI). J Allergy Clin Immunol 2008;121(6):1442-7.
- Iskedjian M, Szajewska H, Spieldenner J, et al. Meta-analysis of a partially hydrolysed 100%-whey infant formula vs. extensively hydrolysed infant formulas in the prevention of atopic dermatitis. Curr Med Res Opin 2010;26(11):2599-606.
- Sampson HA, Bernhisel-Broadbent J, Yang E, Scanlon SM. Safety of casein hydrolysate formula in children with cow milk allergy. J Pediatr 1991;118(4 Pt 1):520-5.
- Terheggen-Lagro SW, Khouw IM, Schaafsma A, Wauters EA. Safety of a new extensively hydrolysed formula in children with cow's milk protein allergy: a double blind crossover study. BMC Pediatr 2002;2:10.
- Ibero M, Bone J, Martin B, Martinez J. Evaluation of an extensively hydrolysed casein formula (Damira 2000) in children with allergy to cow's milk proteins. Allergol Immunopathol (Madr) 2010;38(2):60-8.
- Harrison GG, Graver EJ, Vargas M, et al. Growth and adiposity of term infants fed whey-predominant or casein-predominant formulas or human milk. J Pediatr Gastroenterol Nutr 1987;6(5):739-47.
- Agostoni C, Fiocchi A, Riva E, et al. Growth of infants with IgE-mediated cow's milk allergy fed different formulas in the complementary feeding period. Pediatr Allergy Immunol 2007;18(7):599-606.
- Borschel MW, Ziegler EE, Wedig RT, Oliver JS. Growth of healthy term infants fed an extensively hydrolyzed casein-based or free amino acid-based infant formula: a randomized, double-blind, controlled trial. Clin Pediatr (Phila) 2013;52(10):910-7.
- Borschel MW, Baggs GE, Barrett-Reis B. Growth of healthy term infants fed ready-to-feed and powdered forms of an extensively hydrolyzed casein-based infant formula: a randomized, blinded, controlled trial. Clin Pediatr (Phila) 2014;53(6):585-92.
- Knip M, Virtanen SM, Seppa K, et al. Dietary intervention in infancy and later signs of beta-cell autoimmunity. N Engl J Med 2010;363(20):1900-8.
- Chanson-Rolle A, Aubin F, Braesco V, Hamasaki T, Kitakaze M. Influence of the Lactotripeptides Isoleucine-Proline-Proline and Valine-Proline-Proline on Systolic Blood Pressure in Japanese Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS One. 2015;10(11):e0142235.
- Cicero AFG, Aubin F, Azais-Braesco V, Borghi C. Do the lactotripeptides isoleucine-proline-proline and valine-proline-proline reduce systolic blood pressure in European subjects? A meta-analysis of randomized controlled trials. Am J Hypertens. 2013;26(3):442-9.
- Cicero AFG, Colletti A, Rosticci M, et al. Effect of Lactotripeptides (Isoleucine-Proline-Proline/Valine-Proline-Proline) on Blood Pressure and Arterial Stiffness Changes in Subjects with Suboptimal Blood Pressure Control and Metabolic Syndrome: A Double-Blind, Randomized, Crossover Clinical Trial. Metab Syndr Relat Disord. 2016;14(3):161-6.
- Fekete AA, Givens DA, Lovegrove JA. Casein-derived lactotripeptides reduce systolic and diastolic blood pressure in a meta-analysis of randomised clinical trials. Nutrients. 2015;7(1):659-81.
- Hautaniemi EJ, Tikkakoski AJ, Tahvanainen A, et al. Effect of fermented milk product containing lactotripeptides and plant sterol esters on haemodynamics in subjects with the metabolic syndrome--a randomised, double-blind, placebo-controlled study. Br J Nutr. 2015;114(3):376-86.
- Qin LQ, Xu JY, Dong JY, Zhao Y, van Bladeren P, Zhang W. Lactotripeptides intake and blood pressure management: a meta-analysis of randomised controlled clinical trials. Nutr Metab Cardiovasc Dis. 2013;23(5):395-402.
- Sakata Y, Yoshida C, Fujiki Y, et al. Effects of Casein Hydrolysate Ingestion on Thermoregulatory Responses in Healthy Adults during Exercise in Heated Conditions: A Randomized Crossover Trial. Nutrients. 2020;12(3):867.
- Turpeinen AM, Järvenpää S, Kautiainen H, Korpela R, Vapaatalo H. Antihypertensive effects of bioactive tripeptides-a random effects meta-analysis. Ann Med. 2013;45(1):51-6.
- Horner K, Drummond E, O'Sullivan V, S C Sri Harsha P, Brennan L. Effects of a casein hydrolysate versus intact casein on gastric emptying and amino acid responses. Eur J Nutr. 2019;58(3):955-964.
- Kim HJ, Kim J, Lee S, et al. A Double-Blind, Randomized, Placebo-Controlled Crossover Clinical Study of the Effects of Alpha-s1 Casein Hydrolysate on Sleep Disturbance. Nutrients. 2019;11(7):1466.
- Laatikainen R, Salmenkari H, Sibakov T, Vapaatalo H, Turpeinen A. Randomised Controlled Trial: Partial Hydrolysation of Casein Protein in Milk Decreases Gastrointestinal Symptoms in Subjects with Functional Gastrointestinal Disorders. Nutrients. 2020;12(7):2140.
- Igase M, Okada Y, Igase K, et al. Casein Hydrolysate Containing Milk-Derived Peptides Reduces Facial Pigmentation Partly by Decreasing Advanced Glycation End Products in the Skin: A Randomized Double-Blind Placebo-Controlled Trial. Rejuvenation Res 2021;24(2):97-103.
- Virtanen SM, Cuthbertson D, Couluris M, Savilahti E, Knip M, Krischer JP; TRIGR Investigators. Effect of extensively hydrolyzed casein vs. conventional formula on the risk of asthma and allergies: The TRIGR randomized clinical trial. Pediatr Allergy Immunol 2021;32(4):670-678.
- Tomiyama H, Fujii M, Shiina K, et al. Effects of Lactotripeptide Supplementation on Tele-Monitored Home Blood Pressure and on Vascular and Renal Function in Prehypertension - Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study. Circ Rep 2019;1(10):438-444.
- Thiagarajah K, Chee HP, Sit NW. Effect of Alpha-S1-Casein Tryptic Hydrolysate and L-Theanine on Poor Sleep Quality: A Double Blind, Randomized Placebo-Controlled Crossover Trial. Nutrients 2022;14(3):652.
- Kerure AS, Udare S, Vispute C. Role of Lactium ™ in Psychodermatology: The CERTAIN Trial(#) on Patients with Acne Vulgaris. Dermatol Res Pract 2022;2022:2916317.
- Zhou S, Xu T, Zhang X, Luo J, An P, Luo Y. Effect of Casein Hydrolysate on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2022;14(19):4207.
- Paquete AT, Martins R, Connolly MP, Hegar B, Munasir Z, Stephanus S. Managing Cow's Milk Protein Allergy in Indonesia: A Cost-effectiveness Analysis of Hypoallergenic Milk Formulas from the Private Payers' Perspective. J Health Econ Outcomes Res 2022;9(2):77-85.
- Estrada Reyes E, Zepeda Ortega B, Ten Haaf D, et al. Symptom's resolution and growth outcome of children with cow's milk protein allergy consuming two hydrolyzed formulas: A retrospective study in Mexico. Front Allergy 2023;4:1073430.
