NZ622188B2 - Whey protein micelles to enhance muscle mass and performance - Google Patents

Abstract

Disclosed is a non-therapeutic use of whey protein micelles to enhance muscle protein synthesis in a subject by inducing a delayed hyper-aminoacidemia, wherein the whey protein micelles are administered to the subject in a daily dose of at least 30g dry weight and are provided in combination with a meal, and wherein the meal comprises whey protein isolates, native or hydrolyzed milk proteins, free amino acids, or a combination thereof, wherein the combination of the whey protein micelles and the meal comprises 15-50 wt% proteins, 10-15% wt% lipids, 25-50 wt% carbohydrates, and 5-10 wt% fibres of total dry weight, and wherein the whey protein micelles are administered in the form of a composition comprising free leucine, wherein the free leucine is present in an amount of less than 18% dry weight of the composition, and wherein the composition contains no added vitamin D; and wherein the non-therapeutic use does not require an exercise regimen to enhance muscle protein synthesis in the subject. meal, and wherein the meal comprises whey protein isolates, native or hydrolyzed milk proteins, free amino acids, or a combination thereof, wherein the combination of the whey protein micelles and the meal comprises 15-50 wt% proteins, 10-15% wt% lipids, 25-50 wt% carbohydrates, and 5-10 wt% fibres of total dry weight, and wherein the whey protein micelles are administered in the form of a composition comprising free leucine, wherein the free leucine is present in an amount of less than 18% dry weight of the composition, and wherein the composition contains no added vitamin D; and wherein the non-therapeutic use does not require an exercise regimen to enhance muscle protein synthesis in the subject.

Description

WO 57231 Whey protein micelles to enhance muscle mass and performance The present invention relates to a non-therapeutic use 0: whey n micelles to enhance muscle protein synthesis in a subject. Further aspects 0: the invention are food compositions comprising whey protein micelles to be administered to children, athletes or elderly persons.

Whey n is choice tor individuals I) an excellent protein 0' all ages who value the role 0: a healthy diet in helping to maintain and improve their health, strength and physical mance. Whey prOtein e, the purest jorm avai'ab'e, is still currently unsurpassed as a SOJICG of the essential amino acids required in a daily diet. Essential amino acids are the building blocks for healthy muscles, skin, nails and other body tissues.

US7011/750310 discloses that a whey composition combined with active ingredients such as vitamin Z) can help 11) improve muscular—skeletal health in elderly persons. lowever, vitamin D mentation — i: overdosed — may lead to hypervitaminosis D, and consequertly to a buildup o; calcium in blood (hypercalcemia), which can cause ms such as poor appetite, nausea and vomiting.

Whey prOtein has long been considered the ‘gold standard’ 0: protein jor serious athletes who work hard to develop and sustain a lean, strong and well de:fined physique. Athletes need more protein in their diet, 0 ften as much as twice the recommended daily nce. The protein they choose makes a di""erence and there are several reasons why whey protein is a pre ferred choice for athletes of all types. Whey prOtein is a naturally complete prOtein, containing all the essential amino acids required in an ideal combination to help improve body composition and to enhance athletic performance. Whey protein is a rich source 0: branched chain amino acids (BCAAs). This is importan a for athletes, since those BCAAs are metabolized directly in'to muscle tissue and are ,he first amino acids used during periods 0: exercise and resistance training. Whey protein is also an excellent source of the amino acid leucine.

Leucine is important for athletes as it plays a key role in promoting muscle protein synthesis and muscle growth.

WO20ll/ll2695 describes in this respect a nutritional ition comprising whey protein powder and leucine. It is disclosed that leucine has been found to slow the degradation O muscle tissue by increasing the synthesis 0: muscle proteins in aged rats. lowever, according to /Ll2695 the flavor O" leucine is lly unpleasant when included in doses that are e ous in the stimulation 0" protein sis in .

Indeed, the sensory properties 0" leucine include a bitter mouth taste that is unpleasant to consumers.

Dietary protein is very impor,ant for growth 0 in"ants and children. Whey protein contains many of the same components as can be found in human breast milk and for this reason is a key ingredient in many in ant "ormu'as. y, the l composition 0: the whey n as protein source rich in essential amino acids, BCAAs and leucine, supports the healthy growth and bui:_d-up or muscle tissue for the growing up child, in a very simiI_ar way as it does for athletes.

As we age, muscle loss and its ve health implications is a growing concern. Good nutrition and adequate amounts 0: high quality whey protein can help to maintain strong muscles during aging, especially when combined with physical exercise and resistance training. A recent study found that older men who consumed whey protein showed greater protein synthesis and muscle , which helped to limit loss 0: muscle over time.

Tang JIL-lJ et al. (2009, J Appl Physiol 107:987-992) igated the response 0: skeletal muscle n synthesis in young men following the ingestion of three distinct but high-quality y proteins, i.e. whey, micellar casein and soy, at rest and after resistanc x rcis . Th r by, the authors reported that the consumption 0: whey proteins stimulated muscle prOtein synthesis to a greater degree than casein, both at rest and alter resistance exercise. Whey proteins stimulated also a significantly larger rise in muscle synthesis than soy prOteins, which was in congruence with previous work 0: the same s. They concluded that whey proteins stimulate al muscle protein synthesis to a greater extent than either casein or soy proteins, both at rest and after resistance exercise.

WO?O’l/Oll757 discloses a method of ating the loss 0: functional status comprising a nutritional intervention tha helps prevent the loss 0: muscle mass, said nutritional invention comprising — next to many other active ingredients whey protein; and an exercise regimen.

However, people may be unwilling or unable to perform such an exercise program.

There is still a persisting need in the food industry to find even better nutritional solutions than whey protein isolate to enhance muscle mass, strength and performance for healthy individuals of all age.

Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.

It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

According to one aspect, the present invention provides non-therapeutic use of whey protein micelles to enhance muscle protein synthesis in a subject, n the whey n micelles are administered in the form of a composition comprising leucine in an amount of less than 18% dry weight of the composition and no added vitamin D; and wherein the non-therapeutic use does not include an additional exercise regimen.

Unless the context clearly requires ise, throughout the ption and the claims, the words "comprise", "comprising", and the like are to be ued in an inclusive sense as opposed to an exclusive or tive sense; that is to say, in the sense of "including, but not limited to".

In one embodiment, the present ion provides a non-therapeutic use of whey protein micelles to enhance muscle protein synthesis in a subject.

The whey protein micelles may be administered in the form of a composition, e.g., a food composition.

As it is known that leucine supplementation generates a bitter taste which is considered unpleasant by consumers, it is preferred that the composition ns leucine in an amount of less than 18% dry weight of the composition, less than 15% dry weight of the composition, or less than 12% dry weight of the composition.

The inventors were sed to see that muscle protein synthesis could be achieved by whey n micelles alone, without the addition of leucine. Hence, the ition of the present invention may contain no added leucine.

The present inventors were also sed that muscle protein synthesis could be achieved without n D supplementation eliminating the risk of vitamin D sing.

Hence the composition used the present invention may contain no added vitamin D or no vitamin D at all.

While physical exercise enhances the effect of the present invention, the inventors were surprised to see that enhancing muscle protein synthesis in a subject in accordance with the present invention does not require an additional exercise regimen to be effective.

Hence, in one embodiment the use of the present invention does not include an additional exercise regimen.

In abother aspect, the invention relates to a food composition comprising whey protein micelles, wherein the food composition is to be administered to an athlete, an elderly person, an infant or a child.

"Whey protein es" (WPM) are defined herein as described in EP1839492A1 and as further terized in t C et al. (2010, Soft Matter 6:4876-4884), where they are referred to as whey protein microgels (WPM). ularly, the "whey protein micelles" are the micelles comprised in the whey protein micelles concentrate obtainable by the process as disclosed in EP1839492A1. Therein, the process for the production of whey protein es concentrate comprises the steps of: a) adjusting the pH of a whey protein aqueous solution to a value between 3.0 and 8.0; b) subjecting the aqueous solution to a temperature between 80 and 98°C; and c) trating the dispersion obtained in step b). Thereby, the micelles produced have an extremely sharp size bution, such that more than 80% o: the micelles produced have a size r than 1 micron in diameter and preferably are between 100 II nm and 900 nm in size. The "whey protein micelles can be in liquid concentrate or in powder ‘orm. "mportant'y, the basic micelle strJCture O" the whey proteins is conserved, in the trate, the powder and reconstituted from the powder for example in water. The "whey protein micelles" are physically stable in dispersion, as powder as well as during spray—drying or —drying.

A rapid increase in plasma amino acids is required 'or stimulating muscle protein synthesis at rest and aluer exercise n M et al., 2003, J Physiol 549:635-644). One o: the currently best ons ‘or providing this rapid increase in plasma amino acids is whey prOtein isolate (WPI) (Tang JIL-lJ et al., 2009, J Appl Physiol 107:987-992). A more sustained amino acid response may prolong the increase in ism and muscle protein synthesis by providing amino acid building blocks over a longer period 0" time (Lacroix M et al., 2006, Am J Clin Nutr 84:1070-9). In addition, a more slowly digested protein may suppress protein breakdown (Dangin M et al., 2001, Am J Physiol 780:fi340-fi348), which would have an additional bene it "or ,he net muscle protein balance, i.e. the di""erence between prOtein synthesis and prOtein breakdown. Thus, a n or a mix 0" proteins that would induce the maximal aminoacidemia but during a longer period 0; time would do bOth, i.e. maximally stimulate protein synthesis and suppress prOtein breakdown.

It has now been surprisingly found by the ors that whey protein micelles consumed as part 0: a meal induce the same high plasma aminoacidemia as an iso-caloric and iso- WO 57231 nitrogenous control meal with whey protein isolates (WPZ), but significantly d postprandially by about 30 min with respec, to that ol the control meal. The pea< amino acid concentration (i.e. Cmax) after the whey pro:ein micelles meal was the same as after the W?I meal, and icantly higher than the maximum trations reached after an iso-caloric and iso-nitrogenous mi'k protein or milk casein meal. The results 0: the clinical study are presented in the Example section.

Hence, the ors have found a protein composition which when consumed as part 0" a regular meal induces a delayed but high maximal aminoacidemia in a subject. This hyper— aminoacidemia for a prolonged postprandial period 0" time is mos, "avourable for maxima'ly stimulating muscle protein synthesis, decreasing muscle protein breakdown and therefore maintaining and/or enhancing muscle mass.

"Hyper—aminoacidemia" is an excess 0: amino acids in the tream, the amino acid pool, which can lead to an increase in protein sis and reduction 0: protein breakdown, with an overa'l positive nitrogen balance. y, the positive nitrogen balance indicates more construction or lean tissue than destruction, leading overall to an increase in lean body mass.

Although not wishing to be bound by theory, the inventors think that whey protein micelles as part 0: a meal seem to induce a delayed gastric emptying and to be more slowly digested as compared to native whey pro:eins such as WPI.

Thereby, whey protein mic ll s d liv r :h amino acids more slowly into the peripheral blood circulation.

Figure 1: Plasma concentrations 0: essential amino acids 3 h after the ingestion o: meal replacements comprising whey protein isolate, whey protein micel'es or micellar casein.

Figure 2: Plasma concentrations 0' 'eucine 3 h after the ingestion o: meal replacements comprising whey protein e, whey protein micelles or micellar casein.

Figure 3: Plasma concentrations 0: essential amino acids 3 h after the ingestion o: meal replacements comprising each one of the 7 di""erent ns.

The t ion pertains to a non-therapeutic use or whey protein micelles to enhance muscle protein synthesis in a subject and thereby to increase muscle mass, muscle strength and/or muscle performance. The hyper—aminoacidemia "or a prolonged postprandial period 0" time provided by the inventive use of ,he whey protein micelles is most favourable for maximally stimulating muscle protein synthesis and ,herefore maintaining and/or enhancing muscle mass, resulting in increased muscle strength and performance.

The non-therapeutic use according to the invention is for a human being, preferably an infant, a growing—up child, an e or an y person. \\ '— nfant" means a child under the age 0: 36 months.

"Athlete" means a person sing the natural or acquired traits, such as strength, agility and endurance that are necessary for al exercise or sports, especially those performed in competitive conteth.

"Elderly person" means a person with a chronological age of 65 years or older. "n anus, children who are still in the growing-up phase, es and elderly persons have in common the need 0; elevated muscle protein synthesis: injants for oheir rapid growth and build up of muscle , athle,es "or r building up muscle mass and muscle per:formance, and elderly persons for at least maintaining and compensating the natural loss 0: muscle mass due to aging. {ence i: is those persons who will best gain from ,he current inven':ion.

The non-therapeutic use 0: whey protein micelles according to the ion pertains also to an animal, preterab'y a cat or a dog. Owners 0: animals, particularly those animals In a preferred embodiment, the whey prO':ein micelles are provided to a subjeCt in a daily dose 0: at least 20 g dry weight, preterably O" at least 30 g dry weight. Those doses should assure a su "icient daily quantity for providing the d e "ect to a subject in at least a mid-term period. "n a ‘urther embodiment, the whey n micelles are provided in combination with a meal.

Most meals comprise ns from a milk, plant and/or animal source and hence upon consump':ion lead to a postprandial 2012/070715 increase in aminoacidemia, i.e. I] an elevated concentration 0; amino acids in the plasma 0: the consumer. It is now an advantage, to combine the administration 0: whey protein es in combination with such a meal. Thereby, the pos tprandial plasma amino acid peak resulting from ,he proteins presen, in ,he meal adds up to the postprandial amino acid peak resul, ing from the whey prOtein micelles which are delayed by ca. 3 0 min in respect to the first amino acid peak.

Thereby, the overall resulting hyper—aminoacidemia is extended and nged in time. This in return is most ‘avourable "Ol’ maximal:_y stimul ating muscle protein synthesis and there:fore maintaining or enhancing muscle mass.

In a preferred embodiment, the meal comprises whey protein isolates, native or hydrolyzed milk proteins, free amino acids, or a combination thereo:. As known from earlier studies, a whey prOtein meal exhibits a signi ‘icantly stronger aminoacidemia e ec, on subjec us than jor e a plant n meal. Therefore, ageously I the whey protein es are combined with a meal comprising whey prO':eins in ,he "orm 0‘ WP" or milk. Advantageously I the meal can be even further supplemented with free amino acids in combination with the whey or milk proteins to optimally induce a hyper— aminoacidemia upon consumption 0: said meal. ?re ferably, the combination 0: the whey protein micelles and the meal comprises 15-50 wt% proteins, 10-15 Wt% lipids, 25-50 Wt% carbohydrate s and 5-10 wt% ‘iber o the to ,al dry weight of the combinati OH.

In a pre:ferred embodiment, the whey protein es are provided together and/or as part 0: a meal in the ‘orm 0 a beverage, nutrit ional composition, bar, akes, biscuits OI as pellets. Thereby, the di "erent dual protein components can be optimally dosed for providing a best and prolonged hyper—aminoacidemia "ect 1 e and at the same time optimized :OI a good, organoleptica' 'y best product application.

Furthermore, it is convenien, for a consumer to have the whey prOtein micelles with the meal in one single consumable food product, like for e a ge or bar.

In a second , the invention s to a food composition comprising whey protein micelles, wherein the food composition is to be administered to an athlete or an elderly person. The food composition can for example be in the form 0' a bodybuilding supplement, a SpOIuS nu ,rition bar, a nutrition sports beverage, or a food supplement for seniors. "n a further aspect, the invention relates to a food composition for an i 1'1 fant or a child. The food composition can for example be an in ant "eeding formula, a milk drink or shake, a fermented or acidi fied milk product in the form e.g.

O: a yoghurt or dessert, a biscuit, an ice cream.

In a still further aspect, the invention relates to a food composition for animals comprising whey protein micelles.

Preferably, the food ition is for a cat, a dog, a horse or cattle.

Those ski"ed in the art will understand that they can freely combine a" features 0'' the present :ion disclosed herein. "n particular, features described for the non— therapeutic use may be used and combined with the food compositions, and vice 1 versa. Further, fea cures described :OI di" "erent ments o: the present inven':ion may be combined as well. Further advantages and features 0'' the present invention are apparent from the figures and examples.

Example A randomized double-blind 7-arm crossover study was performed in twenty- three healthy men in the ing way. A test meal replacement was ingested at lunch time on 7 separate occasions separated each by a wash-out period 0: one week. The meal replacements were iso-caloric and trogenous. They were composed of the tested protein (30g, 7.2% w/w), 'ipids , 2.8% w/w), carbohydrates (42.7g, lO.2% w/w) and fibers (6.3g, 1.5% w/w). The tested proteins were: (1) whey protein isolate (WPI); (2) whey prOtein micelles (WPM); (3) extensively hydrolyzed whey prOtein (EHWP); (4) micellar casein (ICP); (5) extensively hydrolyzed casein protein (EHCP); (6) total milk proteins (TMP); and (7) extensively hydrolyzed milk proteins (EHMP). The meal replacements were completed with water to 430mL and ned 388kcal per serving.

Arterialized venous blood samples were taken, via a catheter inserted into a wrist vein 0: the volunteers, before and :or 3h after consuming th t st m al r plac m nt. ?lasma samples were Jsed to analyze amino acids by gas tography and mass speC':rometry. The results are shown in Figures 1 to 3.

Firstly, the results confirmed that intact whey protein induces a higher aminoacidemia than micellar casein. Secondly, it was found that the peaks ol ,he postprandial plasma amino acid concentrations a fter ption of ,he WP: and WPM test meal replacements, gh similar in extent and height, were delayed by approximately 30 min, i.e. occarring at 12 0 min rather than at 90 min. This allowed maintenance 0: an elevated tration 0: plasma amino acids for I) a prolonged period or WO 57231 time after the ingestion o: the whey protein micelles (Figures l to 3: small dotted lines).

Claims (6)

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS: -

1. Non-therapeutic use of whey protein micelles to e muscle protein synthesis in a subject by inducing a delayed hyper-aminoacidemia, wherein the whey 5 protein micelles are administered to the subject in a daily dose of at least 30g dry weight and are provided in combination with a meal, and wherein the meal ses whey protein isolates, native or hydrolyzed milk proteins, free amino acids, or a combination thereof, wherein the combination of the whey protein micelles and the meal ses 15-50 wt% proteins, 10-15% wt% lipids, 25-50 wt% ydrates, and 10 5-10 wt% fibres of total dry weight, and wherein the whey protein micelles are administered in the form of a composition comprising free leucine, wherein the free leucine is present in an amount of less than 18% dry weight of the composition, and wherein the composition contains no added vitamin D; and wherein the erapeutic use does not require an exercise regimen to enhance muscle protein sis in the 15 subject.

2. The non-therapeutic use according to claim 1, to increase muscle mass, muscle strength and/or muscle performance. 20

3. The erapeutic use according to claim 1 or claim 2, wherein the subject is an infant, a g-up child, an athlete or an elderly person.

4. The non-therapeutic use according to claim 1 or claim 2, wherein the subject is an animal, preferably a cat or a dog.

5. The non-therapeutic use according to any one of the claims 1 to 4, wherein the whey protein micelles are provided as part of the meal in the form of a beverage, nutritional composition, bar, flakes, biscuits, or as pellets. 30

6. The non-therapeutic use according to claim 1, substantially as herein described with nce to any one or more of the examples but excluding comparative examples.