Composition for maintaining total amino acid in blood at high concentration

Abstract

To provide a novel composition for maintaining a total amino acid in blood at a high concentration and a novel composition for suppressing a blood sugar spike and / or reactive low hypoglycemia.SOLUTION: According to the present invention, compositions containing fermented milk made from whey protein are provided for maintaining high levels of total amino acids in the blood and for suppressing blood sugar spikes and / or reactive hypoglycemia. Furthermore, compositions containing whey protein for maintaining high levels of total amino acids in the blood and for suppressing blood sugar spikes and / or reactive hypoglycemia are also provided according to the present invention. The present invention is advantageous in that it not only achieves the effect of maintaining high levels of total amino acids in the blood and suppressing blood sugar spikes and reactive hypoglycemia but also has a high safety profile with no concerns about side effects even with prolonged continuous intake.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a composition for maintaining a high concentration of total amino acids in blood. The present invention also relates to a composition for suppressing blood glucose spikes and / or reactive hypoglycemia.

Background Art

[0002] Among nutrients, protein is a constituent component of the body and also plays a role in maintaining skeletal muscle mass. However, when skeletal muscle mass decreases due to aging, disease, etc., it not only threatens healthy life expectancy but may also affect life expectancy itself. For this reason, efficient protein assimilation is required, and it is considered desirable to maintain blood amino acids at a high concentration for a certain period of time in order to create a state in which skeletal muscle is easily synthesized.

[0003] On the other hand, when food is ingested, the sugar contained in the food is decomposed into glucose, causing blood glucose levels to rise. To lower the blood glucose level, insulin is secreted, increasing the blood insulin concentration. However, a rapid increase in blood glucose and blood insulin concentrations, or the continuation of high levels of these values, may damage blood vessels and also lead to insulin resistance, which is not desirable for health. In addition, there is a condition called reactive hypoglycemia, in which blood glucose levels drop more than necessary after a rapid increase in blood glucose, which can also be a factor in reducing quality of life such as headaches and drowsiness (Non-Patent Document 1).

[0004] Under such circumstances, fermented milk for promoting an increase in blood amino acid concentration (Patent Document 1), nutritional composition for increasing skeletal muscle mass (Patent Document 2), composition for suppressing an increase in blood glucose level (Patent Document 3), etc. have been developed so far.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

[0006] [Non-Patent Document 1] Ceriello A, et al., Diabetes, 2008; 57(5): 1349-54. [Summary of the Invention] [Problems to be Solved by the Invention]

[0007] An object of the present invention is to provide a composition for maintaining a high concentration of total blood amino acids and a composition for suppressing a novel blood glucose spike and / or reactive hypoglycemia. [Means for Solving the Problems]

[0008] The present inventors have now found that in a human test, by ingesting fermented milk containing whey protein as a raw material and whey protein, the total blood amino acids are maintained at a high concentration, and the blood glucose spike and reactive hypoglycemia are suppressed. The present invention is based on these findings.

[0009] According to the present invention, the following inventions are provided. [1] A composition for maintaining a high concentration of total blood amino acids, comprising fermented milk containing whey protein as a raw material, wherein the ratio of whey protein to the total protein content in the raw material of the fermented milk is 70% or more, and the total blood amino acid concentration 45 to 90 minutes after ingestion is maintained at 70% or more of the highest total blood amino acid concentration after ingestion. [2] A composition for maintaining a high concentration of total blood amino acids, comprising whey protein, wherein the ratio of whey protein to the total protein content in the composition is 70% or more, and the total blood amino acid concentration 45 to 90 minutes after ingestion is maintained at 70% or more of the highest total blood amino acid concentration after ingestion. [3]A composition for suppressing blood glucose spikes and / or reactive hypoglycemia, comprising fermented milk containing whey protein as a raw material, wherein the ratio of whey protein to the total protein content in the raw material of the fermented milk is 70% or more. [4]A composition for suppressing blood glucose spikes, comprising whey protein, wherein the ratio of whey protein to the total protein content in the composition is 70% or more. [5]The composition according to [1] or [3] above, wherein the fermented milk is fermented by Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus. [6]The composition according to any one of [1] to [5] above, for suppressing the increase in blood glucose level and / or blood insulin concentration after ingestion. [7]When the total blood amino acid concentration 30 minutes to 90 minutes after ingestion is maintained at 350 μM or more higher than the total blood amino acid concentration before ingestion when the subject ingests 10 g or more of the fermented milk (converted as protein amount) or 10 g or more of the whey protein as the intake per meal, the composition according to any one of [1] to [6] above. [8]The composition according to any one of [1] to [7] above, wherein the difference between the maximum blood glucose level after ingestion and the blood glucose level before ingestion is 30 mg / dL or less. [9]The composition according to any one of [1] to [8] above, wherein the blood glucose level 0 minutes to 120 minutes after ingestion is maintained higher than the blood glucose level before ingestion by more than 0 mg / dL.

[10] The composition according to any one of [6] to [9] above, wherein the increase in blood glucose level after ingestion is 30 mg / dL or less when the subject ingests 10 g or more of the fermented milk (converted as protein amount) or 10 g or more of the whey protein as the intake per meal.

[11] The composition according to any one of [6] to

[10] above, wherein the increase in blood insulin concentration after ingestion is 40 μU / mL or less when the subject ingests 10 g or more of the fermented milk (converted as protein amount) or 10 g or more of the whey protein as the intake per meal.

[12] The composition according to any one of [1] to

[10] above, which is a liquid diet.

[0010] The active ingredient of the present invention is fermented milk and / or whey protein containing whey protein that has been used as a food raw material for many years. Therefore, the composition of the present invention has the effects of maintaining a high concentration of total amino acids in the blood and suppressing blood glucose spikes and reactive hypoglycemia, and is advantageous in that there is no concern about side effects even when continuously ingested over a long period of time and it has high safety.

Brief Description of the Drawings

[0011]

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[0012] The present invention is a composition containing whey protein (sometimes referred to as "the unfermented whey composition of the present invention" in this specification). In the present invention, whey protein is also called milk whey protein and is not particularly limited. In the present invention, separated or purified whey protein can be used as the whey protein, and raw materials or food and drink products (for example, milk protein mixtures) that already contain whey protein and casein protein in a specific protein mass ratio can also be used.

[0013] In the present invention, examples of the separated and purified whey protein include whey stock solution (such as sweet whey, acid whey, etc.), its concentrate, its dried product (such as whey powder, etc.), its frozen product, etc., and their reduction solutions, etc. Further, demineralized whey, whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin (α-La), β-lactoglobulin (β-Lg), immunoglobulin, lactoferrin, etc., and their reduction solutions, etc. are also included. In addition, examples of raw materials and food and drink products containing whey protein include raw milk, sterilized milk (such as cow's milk), skim milk, milk with adjusted components, processed milk, dairy products (such as condensed milk, powdered milk, sweetened condensed milk, fermented milk (such as yogurt, etc.), lactic acid bacteria beverages, processed cheeses, ice creams, creams), and milk protein concentrate (MPC: Milk Protein Concentrate), and their concentrates, their dried products, their frozen products, etc. At this time, as the raw materials and food and drink products containing the above-mentioned whey protein, commercially available products may be obtained and used, or they may be prepared and used by oneself.

[0014] In the unfermented whey composition of the present invention, the ratio of whey protein to the content of total protein in the composition is 70% or more, but may also be 71% or more, 72% or more, 73% or more, 74% or more, 75% or more, 76% or more, 77% or more, 78% or more, 79% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100%, and "or more" can mean "exceeding".

[0015] The unfermented whey composition of the present invention can contain proteins other than whey protein. Examples of proteins that can be included in the unfermented whey composition of the present invention include, but are not limited to, casein protein, soy protein, fish meat protein, pea protein, egg protein, etc.

[0016] The present invention also relates to a composition comprising fermented milk containing whey protein as a raw material (hereinafter sometimes referred to as "the fermented whey composition of the present invention" in this specification). In the present invention, "fermented milk" refers to fermented milk, for example, "fermented milk", "lactic acid bacteria beverage", "milk beverage", "natural cheese" and "food mainly made of milk etc." defined in the ordinance on the ingredient standards of milk and dairy products (Ordinance on Milk etc.), but is not limited thereto. For example, fermented milk includes "fermented milk" defined in the Ordinance on Milk etc., that is, milk such as raw milk, cow milk, special cow milk, raw goat milk, pasteurized goat milk, raw ewe milk, adjusted milk, low-fat milk, skim milk and processed milk, or milk containing not less than the same amount of non-fat milk solids as these, fermented with lactic acid bacteria or yeast and made into a solid form (hard type), paste form (soft type) or liquid form (drink type), or those obtained by freezing these, but is not limited thereto.

[0017] The fermented milk contained in the fermented whey composition of the present invention can be obtained as a culture obtained by adding fermenting microorganisms such as lactic acid bacteria to a raw material containing at least whey protein and fermenting it.

[0018] The fermented whey composition of the present invention contains whey protein as a raw material for fermented milk, but the ratio of whey protein to the total protein content in the raw material of the fermented milk is 70% or more, and can also be 71% or more, 72% or more, 73% or more, 74% or more, 75% or more, 76% or more, 77% or more, 78% or more, 79% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more or 100% or more, and "or more" can mean "more than".

[0019] In the fermented whey composition of the present invention, the raw material of the fermented milk can contain proteins other than whey protein. Examples of proteins that can be included in the raw material of the fermented milk include, but are not limited to, casein protein, soy protein, fish meat protein, pea protein, egg protein, and the like.

[0020] In the fermented whey composition of the present invention, as the raw material of the fermented milk, in addition to whey protein, for example, skim milk powder, skim concentrated milk, fresh cream, butter, raw milk, MPC, etc. can be used, although not limited thereto.

[0021] In the present invention, the fermented milk can be obtained by adding a predetermined amount of lactic acid bacteria starter to the raw material of the fermented milk to form a fermentation mix and fermenting it under predetermined fermentation conditions.

[0022] In the present invention, the addition amount of the lactic acid bacteria starter can be determined by a conventional method according to the amount of the raw material of the fermented milk, and for example, it can be 0.01% by mass to 10% by mass, 0.03% by mass to 8% by mass, or 0.05% by mass to 6% by mass.

[0023] In the present invention, the fermentation temperature can be, for example, 30°C to 60°C, preferably 35°C to 55°C, more preferably 40°C to 50°C. The fermentation time can be appropriately set in consideration of the fermentation temperature, and for example, it can be 5 hours to 20 hours, more preferably 6 hours to 18 hours, and even more preferably 7 hours to 15 hours. Also, the above fermentation conditions can be set with the pH (for example, pH 3 to 5, preferably pH 4 to 4.5) at the time when the fermentation progresses and finally becomes an acidified state as a criterion for the completion of fermentation.

[0024] In the present invention, the fermenting microorganism used for the fermentation of whey protein is not particularly limited, and examples include Lactobacillus delbrueckii subsp. bulgaricus ( Lactobacillus delbrueckii subsp. bulgaricus ), Lactococcus lactis ( Lactococuslactis ) Lactobacillus gasseri Lactobacillus gasseri ) Lactobacillus helveticus Lactobacillus helveticus ) and other lactic acid bacteria such as Streptococcus thermophilus Streptococcus thermophilus ) and other lactic acid cocci, bifidobacteria, propionic acid bacteria, yeast, etc., one or more selected from among them can be used. Preferably, a combination of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus can be used. As these specific strains, a combination of Lactobacillus delbrueckii subsp. bulgaricus OLL205013 strain (Accession number: NITE BP-02411) and Streptococcus thermophilus OLS3290 strain (Accession number: FERM BP-19638), or a combination of Lactobacillus delbrueckii subsp. bulgaricus 2038 strain and Streptococcus thermophilus 1131 strain can be used.

[0025] In the present invention, the lower limit value (equal to or exceeding) of the concentration of non-fat milk solids in fermented milk can be, for example, 1% by mass, 1.5% by mass, 2% by mass, 2.5% by mass, 3% by mass, 3.5% by mass, 4% by mass, 4.5% by mass, 5% by mass, 5.5% by mass, 6% by mass, 6.5% by mass, 7% by mass, 7.5% by mass, 8% by mass, 8.5% by mass, 9% by mass, 9.5% by mass, 10% by mass, 10.5% by mass, 11% by mass, 11.5% by mass or 12% by mass, and the upper limit value (equal to or less than) can be, for example, 30% by mass, 29.5% by mass, 29% by mass, 28.5% by mass, 28% by mass, 27.5% by mass, 27% by mass, 26.5% by mass, 26% by mass, 25.5% by mass or 25% by mass. These upper and lower limit values can be arbitrarily combined. For example, it can be 1% by mass or more and 30% by mass or less, 2% by mass or more and 30% by mass or less, 3% by mass or more and 30% by mass or less, 4% by mass or more and 30% by mass or less, 5% by mass or more and 30% by mass or less, 6% by mass or more and 30% by mass or less, 7% by mass or more and 30% by mass or less, 8% by mass or more and 30% by mass or less, 9% by mass or more and 29% by mass or less, 10% by mass or more and 28% by mass or less, 11% by mass or more and 27% by mass or less, or 12% by mass or more and 26% by mass or less.

[0026] In the present invention, the lower limit value (greater than or equal to) of the concentration of milk fat in fermented milk can be, for example, 0.1% by mass, 0.15% by mass, 0.2% by mass, 0.25% by mass, 0.3% by mass, 0.35% by mass, 0.4% by mass, 0.45% by mass, 0.5% by mass, 0.55% by mass, 0.6% by mass, 0.65% by mass, 0.7% by mass, 0.75% by mass, 0.8% by mass, 0.85% by mass, 0.9% by mass, 0.95% by mass or 1.0% by mass, and the upper limit value (less than or equal to) can be, for example, 6% by mass, 5.5% by mass, 5% by mass, 4.5% by mass, 4% by mass, 3.5% by mass, 3% by mass, 2.5% by mass or 2% by mass. These upper and lower limit values can be arbitrarily combined. For example, it can be 0.1% by mass or more and 6% by mass or less, 0.2% by mass or more and 6% by mass or less, 0.3% by mass or more and 6% by mass or less, 0.4% by mass or more and 6% by mass or less, 0.5% by mass or more and 6% by mass or less, 0.6% by mass or more and 5.5% by mass or less, 0.7% by mass or more and 5% by mass or less, 0.8% by mass or more and 4.5% by mass or less, 0.8% by mass or more and 4% by mass or less, 0.9% by mass or more and 3% by mass or less, 1.0% by mass or more and 2.5% by mass or less, or 1% by mass or more and 2% by mass or less.

[0027] In the present invention, the lower limit value (equal to or higher than) of the milk protein concentration in fermented milk can be, for example, 1% by mass, 1.5% by mass, 2% by mass, 2.5% by mass, 3% by mass, 3.5% by mass, 4% by mass, 4.5% by mass, 5% by mass, 5.5% by mass, 6% by mass, 6.5% by mass, 7% by mass, 7.5% by mass, 8% by mass, 8.5% by mass, 9% by mass, 9.5% by mass, 10% by mass, 10.5% by mass, 11% by mass, 11.5% by mass or 12% by mass, and the upper limit value (equal to or lower than) can be, for example, 35% by mass, 34% by mass, 33% by mass, 32% by mass, 31% by mass, 30% by mass, 29% by mass, 28% by mass, 27% by mass, 26% by mass, 25% by mass, 24% by mass, 23% by mass, 22% by mass, 21% by mass, 20% by mass, 19% by mass, 18% by mass, 17% by mass, 16% by mass or 15% by mass. These upper and lower limit values can be arbitrarily combined, for example, 1% by mass or more and 35% by mass or less, 2% by mass or more and 35% by mass or less, 3% by mass or more and 35% by mass or less, 4% by mass or more and 35% by mass or less, 5% by mass or more and 35% by mass or less, 6% by mass or more and 34% by mass or less, 7% by mass or more and 33% by mass or less, 8% by mass or more and 32% by mass or less, 9% by mass or more and 31% by mass or less, 10% by mass or more and 30% by mass or less, 10% by mass or more and 25% by mass or less, 10% by mass or more and 20% by mass or less, or 10% by mass or more and 15% by mass or less. In the present invention, the milk protein concentration in fermented milk can be measured, for example, by the Kjeldahl method.

[0028] The unfermented whey composition and fermented whey composition of the present invention (in this specification, the "unfermented whey composition" and the "fermented whey composition" may be collectively referred to as the "composition of the present invention") may contain fermented milk containing whey protein as an active ingredient and / or components other than whey protein, and such components include, but are not limited to, for example, liquid sugar, saccharides, fats and oils, and the like.

[0029] The composition of the present invention may further contain dietary fiber, stabilizers, lipids, vitamins, minerals, and the like.

[0030] In the composition of the present invention, the dietary fiber is not particularly limited as long as it does not interfere with the effects of the present invention, and examples include edible ones originally present in foods, those obtained by physical, enzymatic, or chemical treatments, or synthetic ones. Also, the dietary fiber may be a high-molecular-weight water-soluble dietary fiber, a low-molecular-weight water-soluble dietary fiber, or an insoluble dietary fiber. Such dietary fibers include polysaccharides such as cellulose, carboxymethyl cellulose, agar, xanthan gum, psyllium seed coat, gellan gum, low-molecular-weight sodium alginate, propylene glycol alginate ester, polydextrose, gum arabic, resistant dextrin, beet fiber, guar gum, enzymatically degraded guar gum, wheat germ, heat-moisture-treated starch (resistant starch), resistant starch, tamarind seed gum, locust bean gum, pullulan, and inulin. Further, examples of the dietary fiber include oligosaccharides such as galactooligosaccharide, fructooligosaccharide, lactulose oligosaccharide, beet oligosaccharide, gentiooligosaccharide, xylooligosaccharide, and soy oligosaccharide, or combinations of these oligosaccharides.

[0031] In the composition of the present invention, examples of the stabilizer include water-soluble soy polysaccharides, cellulose, carboxymethyl cellulose, alginic acid, propylene glycol alginate ester, starch, modified starch, carrageenan, xanthan gum, gellan gum, tamarind seed gum, tara gum, and combinations thereof.

[0032] In the composition of the present invention, the lipid is not particularly limited as long as it can be used for food or pharmaceutical applications, and any lipid may be used. Examples of such lipids include vegetable oils, animal fats and oils, microbial oils, synthetic triglycerides, phospholipids, etc. These may be used alone or in any combination.

[0033] In the composition of the present invention, the vitamin is not particularly limited as long as it can be used for food or pharmaceutical applications, and it may be one kind or a mixture of a plurality of kinds.

[0034] In the composition of the present invention, the mineral is not particularly limited as long as it can be used for food or pharmaceutical applications, and it may be one kind or a mixture of a plurality of kinds.

[0035] As shown in the following examples, the composition of the present invention can maintain a high concentration of total amino acids in the blood as compared with the control group. That is, the composition of the present invention is used to maintain a high concentration of total amino acids in the blood using fermented milk containing whey protein as a raw material and whey protein as an active ingredient. In the present invention, "maintaining a high concentration of total amino acids in the blood" means that when the subject ingests the composition of the present invention, compared with the case where the subject ingests a general liquid diet (not containing fermented milk containing whey protein as a raw material or the ratio of whey protein to total protein is less than 70%) (hereinafter sometimes referred to as "control diet" in this specification), the total amino acids in the blood are maintained at a high concentration. Here, "total amino acids" means 20 kinds of protein-constituting amino acids (isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, histidine, tyrosine, cysteine-cystine, aspartic acid, asparagine, serine, glutamic acid, glutamine, proline, glycine, alanine, and arginine), and "total amino acid concentration" means the total concentration of the above 20 kinds of protein-constituting amino acids.

[0036] When the subject ingests the composition of the present invention, compared with the case where the subject ingests the control diet, for example, the total amino acid concentration in the blood 45 to 90 minutes after ingestion is 1% or more higher, preferably 2% or more, 3% or more, 4% or more, 5% or more, more preferably 6% or more, 7% or more, 8% or more, or 9% or more higher.

[0037] In addition to the above, when the subject ingests the fermented whey composition of the present invention, compared with the case where the subject ingests the control diet, for example, the total amino acid concentration in the blood 45 to 120 minutes after ingestion is 1% or more (preferably 2% or more, 3% or more, or 4% or more) higher, and the total amino acid concentration in the blood 60 minutes to 120 minutes after ingestion is 10% or more (preferably 15% or more, 20% or more, 25% or more, more preferably 30% or more, 35% or more, 40% or more, or 45% or more) higher.

[0038] In addition to the above, when the subject ingests the non-fermented whey composition of the present invention, compared with the case where the subject ingests the control diet, for example, the total amino acid concentration in the blood 60 to 90 minutes after ingestion is 10% or more (preferably 15% or more, 20% or more, 25% or more, more preferably 30% or more, 35% or more, 40% or more, 45% or more, even more preferably 50% or more, 55% or more, 60% or more, or 65% or more) higher.

[0039] The composition of the present invention also, for example, maintains the total amino acid concentration in the blood 45 minutes to 90 minutes after ingestion at 70% or more of the maximum total amino acid concentration in the blood after ingestion of the composition, preferably 71% or more, 72% or more, 73% or more, 74% or more, 75% or more, 76% or more, 77% or more, 78% or more, or 79% or more, more preferably 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, or 89% or more, even more preferably 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, or 95% or more, particularly preferably 96% or more, 97% or more, or 98% or more.

[0040] In addition to the above, the fermented whey composition of the present invention can also be such that the total amino acid concentration in the blood 30 minutes to 120 minutes after ingestion is maintained at 60% or more of the maximum total amino acid concentration in the blood after ingestion of the composition.

[0041] In addition to the above, in the unfermented whey composition of the present invention, the total blood amino acid concentration from 30 minutes to 90 minutes after ingestion is 70% or more (preferably 71% or more, 72% or more, 73% or more, 74% or more, 75% or more, 76% or more, 77% or more, 78% or more or 79% or more, more preferably 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more or 89% or more, still more preferably 90% or more, 91% or more, 92% or more, 93% or more, 94% or more or 95% or more, particularly preferably 96% or more, 97% or more or 98% or more) of the highest total blood amino acid concentration after ingestion of the composition.

[0042] The composition of the present invention also has a total blood amino acid concentration from 30 minutes to 90 minutes after ingestion that is maintained at 350 μM or more higher than the total blood amino acid concentration before ingestion of the composition when the subject ingests 10 g or more of fermented milk (converted as protein content) or 10 g or more of whey protein per meal. It is preferably maintained 360 μM, 370 μM or 380 μM higher, more preferably 390 μM higher, still more preferably 400 μM or more higher. In the present invention, the intake amount of fermented milk and whey protein per meal can be set based on an adult body weight of 65 kg (for example, 10 g or more / body weight 65 kg), and can be appropriately adjusted in consideration of the muscle mass and fat mass of the subject.

[0043] The composition of the present invention also has a total blood amino acid concentration from 45 minutes to 90 minutes after ingestion that is maintained at 350 μM or more higher than the total blood amino acid concentration before ingestion of the composition when the subject ingests 10 g or more of fermented milk (converted as protein content) or 10 g or more of whey protein per meal. It is preferably maintained 360 μM, 370 μM, 380 μM or 390 μM higher, more preferably 400 μM, 410 μM, 420 μM, 430 μM, 440 μM or 450 μM higher, still more preferably 460 μM, 470 μM, 480 μM or 490 μM higher, particularly preferably 500 μM, 510 μM, 520 μM, 530 μM or 540 μM or more higher.

[0044] In addition to the above, in the fermented whey composition of the present invention, the total blood amino acid concentration 30 minutes to 120 minutes after ingestion is 350 μM (preferably 360 μM, more preferably 370 μM) or more higher than the total blood amino acid concentration before ingestion of the composition when the subject ingests 10 g or more of fermented milk (converted as protein content) or 10 g or more of whey protein as the intake amount per meal, and the total blood amino acid concentration 45 minutes to 90 minutes after ingestion is 350 μM (preferably 360 μM, 370 μM, 380 μM or 390 μM, more preferably 400 μM, 410 μM, 420 μM, 430 μM, 440 μM or 450 μM, still more preferably 460 μM, 470 μM, 480 μM or 490 μM) or more higher than the total blood amino acid concentration before ingestion of the composition.

[0045] In addition to the above, in the unfermented whey composition of the present invention, the total blood amino acid concentration 30 minutes to 90 minutes after ingestion is 350 μM (preferably 360 μM, 370 μM, 380 μM or 390 μM, more preferably 400 μM) or more higher than the total blood amino acid concentration before ingestion of the composition when the subject ingests 10 g or more of fermented milk (converted as protein content) or 10 g or more of whey protein as the intake amount per meal, and the total blood amino acid concentration 45 minutes to 90 minutes after ingestion is 350 μM (preferably 360 μM, 370 μM, 380 μM or 390 μM, more preferably 400 μM, 410 μM, 420 μM, 430 μM, 440 μM or 450 μM, still more preferably 460 μM, 470 μM, 480 μM or 490 μM, particularly preferably 500 μM, 510 μM, 520 μM, 530 μM or 540 μM) or more higher than the total blood amino acid concentration before ingestion of the composition.

[0046] The amino acid concentration in blood can be measured by known methods using blood collected from a subject. Such methods include, as shown in the examples described later, the LC / MS / MS method. In addition, as methods using high-performance liquid chromatography (HPLC), amino acids can be derivatized by pre-column derivatization methods (such as the AQC method, OPA method, FMOC method, etc.) or post-column derivatization methods (such as the ninhydrin method, OPA method, etc.), and the derivatized amino acids can be measured by methods using ultraviolet-visible spectrophotometry (UV method), mass spectrometry (MS method, MS / MS method), etc. Here, the method for collecting blood from a subject is not particularly limited, but in order to prevent blood coagulation, a blood anticoagulant may be used. Examples of blood anticoagulants include heparin, sodium citrate, EDTA, etc.

[0047] As shown in the examples described later, fermented milk containing whey protein as a raw material and whey protein have the effect of suppressing blood glucose spikes. That is, the composition of the present invention is used to suppress blood glucose spikes. Here, in the present invention, "blood glucose spike" represents a form of postprandial blood glucose transition, meaning a state in which the postprandial blood glucose level rapidly rises and then rapidly drops. When a blood glucose spike occurs, it causes damage to blood vessels and also leads to insulin resistance, which is not favorable for health.

[0048] When the composition of the present invention is ingested, the difference between the maximum blood glucose level after ingestion and the blood glucose level before ingestion is 30 mg / dL or less, preferably 29 mg / dL or 28 mg / dL, more preferably 27 mg / dL or 26 mg / dL, and even more preferably 25 mg / dL, when the subject ingests 10 g or more of fermented milk (converted as the protein content) or 10 g or more of whey protein per meal as the intake amount per meal.

[0049] As shown in the following examples, fermented milk containing whey protein as a raw material has an effect of suppressing reactive hypoglycemia. That is, the fermented whey composition of the present invention is used for suppressing reactive hypoglycemia. Here, in the present invention, "reactive hypoglycemia" refers to postprandial hypoglycemia, which means a hypoglycemic state caused by a sharp drop in blood glucose level after a sharp rise in postprandial blood glucose level to a level lower than the fasting blood glucose level before meals.

[0050] The fermented whey composition of the present invention is such that the blood glucose level from 0 minutes to 120 minutes after ingestion does not become lower than the blood glucose level before ingestion. Specifically, it is maintained higher than the blood glucose level before ingestion by more than 0 mg / dL, preferably 0.1 mg / dL, 0.2 mg / dL, 0.3 mg / dL, 0.4 mg / dL or 0.5 mg / dL, more preferably 0.6 mg / dL, 0.7 mg / dL, 0.8 mg / dL, 0.9 mg / dL or 1.0 mg / dL, and even more preferably maintained higher than 1.1 mg / dL, 1.2 mg / dL or 1.3 mg / dL.

[0051] As shown in the following examples, fermented milk containing whey protein as a raw material and whey protein have an effect of suppressing the increase in blood glucose level after ingestion. That is, the composition of the present invention is used for suppressing the increase in blood glucose level.

[0052] The composition of the present invention is such that the increase in blood glucose level after ingestion is 30 mg / dL or less, preferably 29 mg / dL or 28 mg / dL, more preferably 27 mg / dL or 26 mg / dL, and even more preferably 25 mg / dL or less.

[0053] In the present invention, the blood glucose level can be measured by a known method. Examples of such methods include hexokinase UV method, FAD-GDH enzyme electrode method, GOD enzyme electrode method, GOD enzyme colorimetric method, GOD-POD colorimetric method, enzyme electrode method using coulometry, quinoprotein glucose dehydrogenase enzyme colorimetric method, quinoprotein glucose dehydrogenase enzyme electrode method, etc.

[0054] As shown in the following examples, fermented milk containing whey protein as a raw material and whey protein have the effect of suppressing the increase in blood insulin concentration after ingestion. That is, the composition of the present invention is used to suppress the increase in blood insulin concentration.

[0055] When the composition of the present invention is ingested, the increase in blood insulin concentration is 40 μU / mL or less, preferably 39 μU / mL or less, more preferably 38 μU / mL or less, and even more preferably 37 μU / mL or less when the subject ingests 10 g or more of fermented milk (converted as the amount of protein) or 10 g or more of whey protein per meal.

[0056] In the present invention, the blood insulin concentration can be measured by a known method. Examples of such methods include ELISA method, chemiluminescence immunoassay (CLIA method), chemiluminescent enzyme immunoassay (CLEIA), etc.

[0057] The composition of the present invention can be provided in the form of pharmaceuticals and quasi-drugs (e.g., pharmaceutical compositions), foods (e.g., food compositions), feeds (e.g., pet foods), etc., and can be implemented according to the following description.

[0058] The composition of the present invention can be orally administered or orally ingested to humans and non-human mammals (e.g., pet animals such as dogs and cats, livestock such as cows and horses). Oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, and suspensions. These preparations can be formulated using pharmaceutically acceptable carriers by methods commonly used in the art. Pharmaceutically acceptable carriers include excipients, binders, diluents, additives, flavors, buffers, thickeners, coloring agents, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, etc.

[0059] When providing the composition of the present invention as a food, fermented milk containing whey protein as a raw material or whey protein can be directly contained in the food, and the food is a fermented milk containing whey protein as a raw material or a food containing an effective amount of whey protein. Here, "containing an effective amount" of fermented milk containing whey protein as a raw material or whey protein means a content such that when the amount normally consumed in each individual food is ingested, fermented milk containing whey protein as a raw material or whey protein is ingested within the range described below. Also, "food" is used in the sense of including health foods, functional foods, health functional foods (for example, foods for specified health uses, nutritional functional foods, foods with functional claims), special-purpose foods (for example, foods for infants, foods for pregnant and lactating women, foods for patients), and supplements.

[0060] In the unfermented whey composition of the present invention, the lower limit value (greater than or equal to) of the content of whey protein (converted as the amount of protein per serving) can be, for example, 1 g, 2 g, 3 g, 4 g, 5 g, 6 g, 7 g, 8 g, 9 g, or 10 g, and the upper limit value (less than or equal to) can be, for example, 50 g, 45 g, 40 g, 35 g, 30 g, 25 g, or 20 g. These lower limit values and upper limit values can be arbitrarily combined, for example, 1 g or more and 50 g or less, 2 g or more and 45 g or less, 3 g or more and 40 g or less, 4 g or more and 35 g or less, or 5 g or more and 30 g or less.

[0061] In the fermented whey composition of the present invention, the lower limit value (greater than or equal to) of the content of fermented milk (converted as the amount of protein per serving) can be, for example, 1 g, 2 g, 3 g, 4 g, 5 g, 6 g, 7 g, 8 g, 9 g, or 10 g, and the upper limit value (less than or equal to) can be, for example, 50 g, 45 g, 40 g, 35 g, 30 g, 25 g, or 20 g. These lower limit values and upper limit values can be arbitrarily combined, for example, 1 g or more and 50 g or less, 2 g or more and 45 g or less, 3 g or more and 40 g or less, 4 g or more and 35 g or less, or 5 g or more and 30 g or less.

[0062] The form of the "food" is not particularly limited, and any form may be used as long as it is a fermented milk containing whey protein as an active ingredient of the present invention or a food capable of containing whey protein. For example, it may be a food for daily intake or a supplement, may be in the form of a beverage, may be in a semi-liquid or gel form (e.g., enteral and oral nutritional foods such as liquid foods and semi-liquid foods), or may be in a solid form. Specific foods include dairy products such as prepared milk powder, milk beverages, fermented milk, and cheese.

[0063] A preferred form of the composition of the present invention is a comprehensive nutritional food. Comprehensive nutritional foods contain nutritional components such as vitamins, minerals, and dietary fiber in addition to the three major nutrients of protein, fat, and carbohydrates. Considering the energy balance, they are often used by consumers who cannot obtain sufficient nutrition from normal diet alone to efficiently intake nutrition. As one form of comprehensive nutritional foods, for example, liquid foods can be mentioned. Note that "liquid food" is a general term for thick liquid foods and enteral nutritional agents. In addition, the nutritional composition of general-purpose liquid foods generally contains nutrients to be ingested as food in a well-balanced manner, and the energy is often designed to be 0.6 - 2.0 kcal / mL. The breakdown of the energy balance can be designed based on, for example, the Japanese dietary intake standards, with protein being about 13 - 20%, fat being about 20 - 30%, and carbohydrates being about 50 - 60%. Other nutritional components are formulated with all the nutrients described in the Japanese dietary intake standards.

[0064] The food of the present invention may be labeled to have an effect of maintaining a high concentration of total amino acids in the blood, an effect of suppressing postprandial blood glucose spikes and / or reactive hypoglycemia, and an effect of suppressing the increase in postprandial blood glucose and / or blood insulin concentration. In this case, for easy understanding by consumers, the food of the present invention may be labeled with, for example, some or all of the following. · Keep the blood amino acid concentration high · Maintain a high concentration of blood amino acids · For those who are concerned about postprandial hyperglycemia (blood glucose spike) · Care for sudden increase in blood glucose level ·Care for rapid decrease in blood glucose level ·Gradually reduce the increase in blood glucose level ·Gradually reduce the decrease in blood glucose level ·Gradually increase the blood insulin concentration

[0065] According to another aspect of the present invention, there is provided a method for maintaining a high concentration of total amino acids in blood, a method for suppressing blood glucose spikes and / or reactive hypoglycemia, and a method for suppressing the increase in blood glucose level and / or blood insulin concentration after ingestion, which comprises causing a fermented milk containing whey protein as a raw material and / or allowing a human or non-human animal to ingest or administer whey protein. The method of the present invention can be carried out according to the description of the composition of the present invention.

[0066] According to another aspect of the present invention, there is also provided the use of whey protein for the production of a composition for maintaining a high concentration of total amino acids in blood, for suppressing blood glucose spikes and / or reactive hypoglycemia, and for suppressing the increase in blood glucose level and / or blood insulin concentration after ingestion. The use of the present invention can be carried out according to the description of the composition and the method of the present invention.

[0067] The method and use of the present invention may be used in mammals including humans, and both therapeutic and non-therapeutic uses are contemplated. As used herein, "non-therapeutic" means not including the act of operating on, treating, or diagnosing a human (i.e., a medical act on a human), specifically, not including a method of operating on, treating, or diagnosing a human by a physician or a person under the instruction of a physician.

Examples

[0068] The present invention will be described more specifically based on the following examples, but the present invention is not limited to these examples.

[0069] Example 1: Effect of whey protein on total blood amino acid concentration, etc. In Example 1, in a human test, the effects of a liquid diet containing whey protein on the total amino acid concentration in blood and the like were examined. (1) Method A Liquid diet containing whey protein Each liquid diet base having the composition shown in Table 1 was prepared according to a conventional method and diluted with water to obtain each liquid diet. In the preparation of the fermented milk shown in Table 1, as the lactic acid bacteria starter, Lactobacillus delbrueckii subsp. bulgaricus Lactbacillus delbrueckii subsp. bulgaricus ) OLL205013 strain (Accession number: NITE BP-02411) and Streptococcus thermophilus Streptococus thermophilus ) OLS3290 strain (Accession number: FERM BP-19638) were used. The nutritional compositions of each liquid diet are shown in Table 2.

[0070] [Table 1]

[0071] [Table 2]

[0072] II Human test A double-blind randomized three-period three-group crossover test was conducted on 16 male subjects. The subjects were randomly divided into three groups, and on the first, second, and third test days, they were made to ingest any one of the fermented milk liquid diet (fermented whey protein group (fermented Whey group)), unfermented milk liquid diet (unfermented whey protein group (unfermented Whey group)), and general liquid diet (control group) prepared in A above in different orders. The specific procedure of the human test is shown in Table 3. Also, statistical comparative studies were conducted as paired tests between (i) the two groups of the fermented Whey group and the control group, and (ii) the two groups of the unfermented Whey group and the control group.

[0073] [Table 3]

[0074] Measurement of total amino acid concentration in blood The total amino acid concentration of the blood specimen collected in [I] above was measured by the following procedures (i) and (ii) using LC / MS / MS. (i) Sample for analysis The blood specimen collected in [I] above was diluted 8-fold with water and mixed 1:1 with a trichloroacetic acid (TCA) solution containing an internal standard mixture of stable isotopes of 20 types of amino acids (Wako APDS tag Wako amino acid internal standard mixture), followed by centrifugation at 12,000 rpm, 4°C for 10 minutes to remove proteins. 100 μL of the obtained supernatant was added to a plate with a filter and centrifuged at 1,000 g, 4°C for 5 minutes, and the obtained sample was used for LC / MS / MS analysis as a sample for analysis. (ii) LC / MS / MS analysis LC / MS / MS analysis was performed under the conditions shown in Table 4. A calibration curve was prepared using pure products, and after correcting the peak area of each amino acid with an internal standard, the concentration of each amino acid was measured from the calibration curve. Then, the total amino acid concentration was calculated by summing the concentrations of each amino acid.

[0075] [Table 4]

[0076] Measurement of blood glucose level and blood insulin concentration The blood glucose level and insulin concentration of the blood specimen collected in [I] above were measured by an external analytical institution (BM&L Co., Ltd.).

[0077] Calculation of ΔCt, ΔCt max, and ΔAUC Regarding the total amino acid concentration in blood, the difference obtained by subtracting the measured value before test meal ingestion (0 minutes) from the measured value at each blood sampling time point was defined as ΔCt, the maximum value thereof as ΔCt max, and the area under the curve of ΔCt from 0 to 120 minutes (ΔAUC (Area Under Curve)) was calculated. Also, regarding the blood glucose level and blood insulin concentration, the difference obtained by subtracting the measured value before test meal ingestion (0 minutes) from the measured value at each blood sampling time point was calculated as ΔCt.

[0078] (2) Results The results were as shown in Figs. 1 - 6 and Tables 5 - 13. In the fermented Whey group, compared with the control group, the ΔAUC of total amino acids in the blood was significantly higher (Fig. 1A), and the ΔCt of total amino acids in the blood from 60 to 120 minutes after ingestion was significantly higher (Fig. 1B). In the fermented Whey group, the ΔCt / ΔCt max of total amino acids in the blood from 30 to 120 minutes after ingestion also exceeded 60%, and the ratio of ΔCt to the ΔCt of the control group (Table 7) from 45 to 120 minutes after ingestion exceeded 100% (Table 5). From these results, it was shown that the fermented whey protein maintained a high concentration of total amino acids in the blood.

[0079] In the unfermented Whey group, compared with the control group, the ΔAUC of total amino acids in the blood tended to be high (Fig. 2A), and the ΔCt of total amino acids in the blood from 60 to 90 minutes after ingestion was significantly higher (Fig. 2B). In the unfermented Whey group, the ΔCt / ΔCt max of total amino acids in the blood from 30 to 90 minutes after ingestion also exceeded 70%, and the ratio of ΔCt to the ΔCt of the control group (Table 7) from 45 to 90 minutes after ingestion exceeded 100% (Table 6). From these results, it was shown that the unfermented whey protein maintained a high concentration of total amino acids in the blood.

[0080] In the fermented Whey group, the peak blood glucose level after ingestion (30 minutes after ingestion) was 75% of that of the control group, and the ΔCt of blood glucose exceeded 0 throughout 15 - 120 minutes after ingestion (Fig. 3, Table 8). From this result, it was shown that the fermented whey protein suppressed blood glucose spikes and reactive hypoglycemia.

[0081] In the unfermented Whey group, the peak blood glucose level after ingestion (30 minutes after ingestion) was 81% of that of the control group (Fig. 4, Table 9). From this result, it was shown that the unfermented whey protein suppressed blood glucose spikes.

[0082] In the fermented whey group, the maximum blood insulin concentration after ingestion (45 minutes after ingestion) was 75% of that in the control group (Figure 5, Table 11). From this result, it was shown that the increase in blood insulin concentration was suppressed by the fermented whey protein.

[0083] In the unfermented whey group, the maximum blood insulin concentration after ingestion (45 minutes after ingestion) was 92% of that in the control group (Figure 6, Table 12). From this result, it was shown that the increase in blood insulin concentration was suppressed by the unfermented whey protein.

[0084]

Table 5

[0085]

Table 6

[0086]

Table 7

[0087]

Table 8

[0088]

Table 9

[0089]

Table 10

[0090]

Table 11

[0091]

Table 12

[0092]

Table 13

Industrial Applicability

[0093] According to the present invention, it becomes possible to provide a method for producing a food product for maintaining a high concentration of total amino acids in blood and for suppressing blood glucose spikes and / or reactive hypoglycemia, with whey protein as an active ingredient.

Claims

1. A composition for maintaining a high concentration of total amino acids in blood, comprising fermented milk containing whey protein as a raw material, wherein the ratio of whey protein to the total protein content in the raw material of the fermented milk is 70% or more, and the total amino acid concentration in blood from 45 minutes to 90 minutes after ingestion is maintained at 70% or more of the highest total amino acid concentration in blood after ingestion.

2. A composition for maintaining a high concentration of total amino acids in blood, comprising whey protein, wherein the ratio of whey protein to the total protein content in the composition is 70% or more, and the total amino acid concentration in blood from 45 minutes to 90 minutes after ingestion is maintained at 70% or more of the highest total amino acid concentration in blood after ingestion.

3. A composition for suppressing a blood glucose spike and / or reactive hypoglycemia, comprising fermented milk containing whey protein as a raw material, wherein the ratio of whey protein to the total protein content in the raw material of the fermented milk is 70% or more.

4. A composition for suppressing a blood glucose spike, comprising whey protein, wherein the ratio of whey protein to the total protein content in the composition is 70% or more.

5. The composition according to claim 1 or 3, wherein the fermented milk is fermented by Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus.

6. The composition according to claim 1 or 2, for suppressing the increase in blood glucose level and / or blood insulin concentration after ingestion.

7. The composition according to claim 1 or 2, wherein the total amino acid concentration in blood from 30 minutes to 90 minutes after ingestion is maintained at 350 μM or more higher than the total amino acid concentration in blood before ingestion when the subject ingests 10 g or more of the fermented milk (converted as protein amount) or 10 g or more of the whey protein as the intake per meal.

8. The composition according to claim 3 or 4, wherein the difference between the highest blood glucose level after ingestion and the blood glucose level before ingestion is 30 mg / dL or less.

9. The composition according to claim 3 or 4, wherein the blood glucose level from 0 minute to 120 minutes after ingestion is maintained at more than 0 mg / dL higher than the blood glucose level before ingestion.

10. The composition according to claim 6, wherein the increase in blood glucose level after ingestion is 30 mg / dL or less when the subject ingests 10 g or more of the fermented milk (converted as the amount of protein) or 10 g or more of the whey protein as the intake amount per meal.

11. The composition according to claim 6, wherein the increase in blood insulin concentration after ingestion is 40 μU / mL or less when the subject ingests 10 g or more of the fermented milk (converted as the amount of protein) or 10 g or more of the whey protein as the intake amount per meal.

12. The composition according to claim 1 or 2, which is a liquid diet.

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