Use of whey protein micelles for infants at risk of obesity or diabetes

Abstract

The invention relates to whey protein micelles for use in the treatment and/or prevention of a disorder linked to an increase in insulin secretion and/or plasma IGF-1 concentration in an infant at risk of developing obesity or diabetes. The invention also relates to a nutritional composition for infants comprising whey protein micelles. Further, the invention relates to a non-therapeutic use of a nutritional composition for infants, comprising whey protein micelles.

Claims

1. A method for the treatment of a disorder linked to an increase in insulin secretion and/or plasma IGF-1 concentration in an infant at risk of developing obesity or diabetes, the method comprising: administering to the infant a composition comprising whey protein micelles, wherein the whey protein micelles constitute at least 30% of the protein source of the infant's daily diet, wherein a protein content of the composition ranges from 1.4 to 3.8 g per 100 kcal, and wherein the composition decreases insulin responses after ingestion of a meal relative to a composition containing an equal amount of whey protein isolates or whey protein hydrolysates.

2. The method according to claim 1, wherein the disorder is selected from the group consisting of obesity, insulin resistance, metabolic syndrome, glucose intolerance and type-2 diabetes.

3. The method according to claim 1, wherein the infant is from birth to the age of 36 months.

4. A method for the treatment of a disorder linked to an increase in insulin secretion and/or plasma IGF-1 concentration in an infant age 0-36 months, the method comprising: administering to the infant whey protein micelles, wherein the whey protein micelles constitute at least 30% of the protein source of the infant's daily diet, wherein a protein content of the composition ranges from 1.4 to 3.8 g per 100 kcal, and wherein the whey protein micelles decrease insulin responses after ingestion of a meal relative to a composition containing an equal amount of whey protein isolates or whey protein hydrolysates.

5. The method according to claim 4, wherein the disorder is selected from the group consisting of obesity, insulin resistance, metabolic syndrome, glucose intolerance and type-2 diabetes.

6. The method according to claim 4, further comprising administering casein.

7. The method according to claim 6, wherein the whey-to-casein weight ratio is between 80:20 and 40:60.

8. The method according to claim 4, wherein the whey protein micelles constitute from 80 to 100% of a protein content of a nutritional composition administered to the infant.

9. A method of decreasing insulin secretion and/or plasma IFG-1 concentration in an infant in need thereof, the method comprising: administering to the infant a composition comprising whey protein micelles to the infant wherein the whey protein micelles constitute at least 30% of the protein source of the infant's daily diet, wherein a protein content of the composition ranges from 1.4 to 3.8 g per 100 kcal, and wherein the composition decreases insulin responses after ingestion of a meal relative to a composition containing an equal amount of whey protein isolates or whey protein hydrolysates.

10. The method of claim 1, wherein the infant is an infant born to an obese, overweight, or diabetic mother.

Description

(1) FIG. 1: Plasma concentrations of insulin 3 h after the ingestion of the 3 meal replacements in healthy human subjects.

(2) FIG. 2: Plasma concentrations of glucose 3 h after the ingestion of the 3 meal replacements in healthy human subjects.

(3) FIG. 3: Plasma concentrations of essential amino acids 3 h after the ingestion of the 3 meal replacements in healthy human subjects.

(4) The present invention pertains to whey protein micelles for use in the treatment and/or prevention of a disorder linked to an increase in insulin secretion and/or plasma IGF-1 concentration in an infant at risk of developing obesity or diabetes. The disorder may be selected from the group consisting of obesity, insulin resistance, metabolic syndrome, glucose intolerance and type-2 diabetes.

(5) For example the disorder may also be selected from the group consisting of insulin resistance, metabolic syndrome, glucose intolerance and type-2 diabetes.

(6) The mechanisms by which growth patterns in infancy may affect obesity risks later in life are not completely understood. A role for insulin and insulin-like growth factor 1 (IGF-1) has been proposed (Koletzko B, von Kries R, Closa R, et al. Can infant feeding choices modulate later obesity risk? Am J Clin Nutr 2009; 89:1502S-8S). In addition to promoting growth, increases in these hormones could stimulate adipogenic activity and adipocyte differentiation thereby increasing susceptibility to overweight and obesity at a later age.

(7) The whey protein micelles of the invention are to be administered to the infant from birth to the age of 36 months.

(8) In a preferred embodiment, the whey protein micelles for use according to the invention constitute at least 30% of the protein source of the infant's daily diet. Thereby, preferably at least 40%, and more preferably at least 50% of the protein source are whey protein micelles. Advantageously and in order to be most effective, a good part of the infant's daily protein source are whey protein micelles.

(9) In a further aspect, the invention relates to a nutritional composition for infants for use in the treatment and/or prevention of a disorder linked to an increase in insulin secretion and/or plasma IGF-1 concentration, wherein the nutritional composition comprises whey protein micelles, and wherein the disorder is selected from the group consisting of obesity, insulin resistance, metabolic syndrome, glucose intolerance and type-2 diabetes.

(10) In a preferred embodiment, the nutritional composition of the invention further comprises casein. The advantages of adding casein to the nutritional composition is to better mimic human milk. The human milk composition starts with a whey-to-casein ratio of about 80:20 to decrease to about 50:50 in very mature milk. Mimicking human milk brings several advantages on having a closer amino acid composition to human milk, on improving thereby the health benefits, the energy balance, the taste and possibly the product stability. Preferably, the nutritional composition comprises casein, wherein the whey-to-casein weight ratio is between 80:20 and 20:80, or between 70:30 and 30:70, or between 60:40 and 40:60.

(11) In an alternative embodiment, the nutritional composition comprises whey protein micelles in a range from 80% to 100% of the total protein content of the nutritional composition. Such compositions contain a higher amount of whey proteins as can typically be found in standard infant formulae. The nutritional composition thereby comes closer in its milk protein composition to early phase human milks. Advantageously, such nutritional compositions are provided to pre-term born infants and/or infants suffering from IUGR.

(12) The nutritional composition of the invention has a total protein content ranging from 1.4 to 3.8 g per 100 kcal.

(13) A further aspect of the invention is a non-therapeutic use of a nutritional composition for infants comprising whey protein micelles, to decrease insulin secretion and/or plasma IFG-1 concentration in a healthy infant.

(14) It is an advantage of the present invention that a nutritional composition comprising whey protein micelles can also be administered to infants who are healthy and/or are not at risk of developing obesity or diabetes later in life. In fact, the nutritional composition as disclosed herein provides also healthy formula-fed infants with a lower plasma insulin and IGF-1 concentration in comparison with infants fed a standard infant formula. Thereby, the nutritional health and hormonal status of infants fed a whey protein micelles comprising composition is closer to breastfed infants than those fed a traditional, standard infant formula. It is well recognized today that human milk is still the best nutrition for infants and serves as gold standard for all developments of new infant nutrition. So far, however, no infant formula is capable of fully mimicking postprandial plasma concentrations of insulin and fasting plasma concentrations of IGF-1 to the concentrations observed in breastfed infants. The nutritional composition of the invention is a step closer to the gold standard.

(15) Further, the invention relates to an infant feeding formula comprising whey protein micelles.

(16) Particularly, the invention relates to an infant feeding formula comprising whey protein micelles, wherein the content of whey protein micelles ranges from 0.4 to 3.8 g per 100 kcal, preferably from 0.8 to 2.7 g per 100 kcal.

(17) Those skilled in the art will understand that they can freely combine all features of the present invention disclosed herein. In particular, features described for the therapeutic use of the whey protein micelles may be combined with the therapeutic and non-therapeutic uses of the nutritional compositions and vice versa. Further, features described for different embodiments of the present invention may be combined. Further advantages and features of the present invention are apparent from the figures and examples.

EXAMPLE

(18) A randomized double-blinded crossover study was performed in twenty-three healthy human subjects. The subjects ingested different meal replacements at lunch time, followed by a wash-out period of one week. A catheter was inserted in the arm of the subjects and served for collecting arterialized blood postprandial for 3 h. Plasma from the blood samples was used to analyze hormones (insulin, c-peptide and glucagon), glucose and amino acids.

(19) The 3 meal replacements tested were iso-caloric and iso-nitrogenous. They were composed of the tested protein (30 g, 7.2% w/w), lipids (11.7 g, 2.8% w/w), carbohydrates (42.7 g, 10.2% w/w) and fibers (6.3 g, 1.5% w/w). The tested proteins were: (1) whey protein isolates (WPI); (2) whey protein micelles (WPM); and (3) extensively hydrolyzed whey protein (EHWP). The meal replacements were completed with water to 420 mL and contained 388 kcal as energy intake.

(20) The results showed a significant decrease of the Cmax (maximal concentration, P=0.015) of insulin responses after the ingestion of the WPM compared with the WPI and EHWP meal replacements. FIG. 1 showed the postprandial insulin responses after the meal replacement ingestion. The postprandial responses of glucose were similar between the meal replacements (FIG. 2). Surprisingly, the WPM meal replacement induced the lowest concentration of plasma amino acids 30 min after the meal ingestion, as opposed to the other protein meals (FIG. 3). The WPM exhibited the lowest rate of appearance of amino acids (especially essential amino acids) in the systemic blood circulation. These lowest plasma amino acids probably participate in lowering the plasma insulin, c-peptide and glucagon (not shown) responses of the WPM at 30 min, the time of insulin Cmax.

(21) FIG. 1-3: small dotted lines represent the whey protein micelles.

(22) This study shows an advantage of WPM in lowering plasma insulin and other hormone compared with WPI in healthy human subjects.