JP7688866B2 - Agent and method for increasing muscle mass percentage, and agent and method for decreasing body fat percentage - Google Patents

Description

The present invention relates to an agent for increasing muscle mass percentage, increasing body water percentage, and decreasing body fat percentage, which contains 1-kestose as an active ingredient.

1-kestose is a trisaccharide oligosaccharide consisting of one glucose molecule and two fructose molecules. 1-kestose is also found in vegetables and grains such as onions, garlic, barley, and rye, and has been consumed since ancient times. It has also been found to be extremely safe, as no toxicity has been found in mutagenicity tests, acute toxicity tests, subchronic toxicity tests, or chronic toxicity tests (Non-Patent Document 1).

1-kestose also has high solubility and heat resistance equivalent to those of sucrose, and its sweetness is about one-third that of sucrose, giving it a pleasant sweetness similar to that of sucrose. Furthermore, it has been reported to have a variety of useful physiological effects, such as suppressing allergies (Patent Document 1) and suppressing the bacterial counts of Fusobacterium and Staphylococcus aureus bacteria, which have been suggested as causative microorganisms of acute hemorrhagic diarrhea in dogs (Patent Document 2).

Patent No. 4162147 International Publication No. 2019/054396

Food and Development, Vol. 49, No. 12, p. 9, 2014

As described above, 1-kestose is a substance that is extremely safe, easy to handle, and has excellent physical properties, but its physiological effects have not been fully elucidated. The present invention has been made to solve this problem, and aims to discover a new physiological effect of 1-kestose and, thereby, provide a new use for 1-kestose.

As a result of intensive research, the inventors have discovered that a new physiological effect of 1-kestose is that it increases muscle mass. They have also found that 1-kestose increases the amount of water in the body. They have also found that 1-kestose reduces the body fat percentage. Based on these findings, they have completed the following inventions.

(1) The muscle mass ratio increasing agent of the present invention contains 1-kestose as an active ingredient.

(2) The muscle mass percentage increasing agent of the present invention can be used to prevent or improve sarcopenia.

(3) The muscle mass percentage increase agent of the present invention can also be used to reduce body fat percentage.

(4) The agent for increasing the body's water content according to the present invention contains 1-kestose as an active ingredient.

(5) The agent for increasing the body's water content according to the present invention can be used to prevent or improve dehydration.

(6) The body fat reduction agent of the present invention contains 1-kestose as an active ingredient.

According to the present invention, novel uses of 1-kestose are provided, including "increasing muscle mass percentage," "preventing or improving sarcopenia," "increasing muscle mass percentage and decreasing body fat percentage," "increasing body water percentage," "preventing or improving dehydration," and "decreasing body fat percentage."

As described above, 1-kestose is highly water-soluble and has good sweetness quality, and therefore can be easily ingested daily either as it is or as a seasoning such as a sweetener, and can also be easily incorporated into various foods, medicines, feed, etc. Therefore, according to the present invention, it is possible to obtain an agent for increasing muscle mass percentage, an agent for preventing or improving sarcopenia, an agent for increasing muscle mass and decreasing body fat percentage, an agent for increasing body water percentage, an agent for preventing or improving dehydration, and an agent for decreasing body fat percentage, which are highly safe and can be easily ingested daily either as it is or by being easily incorporated into various foods, medicines, feed, etc.

According to the present invention, it is possible to increase the muscle mass ratio in the body of a human or animal. As shown in the examples described below, according to the present invention, it is possible to increase skeletal muscle without the need for exercise (resistance exercise) that places a load on the muscles. Therefore, even frail people and elderly people who have difficulty with resistance exercise can improve or maintain their physical abilities. In particular, according to the present invention, it is possible to contribute to the prevention or improvement of sarcopenia (a condition in which muscle mass is reduced and muscle strength and physical function are reduced). Furthermore, according to the present invention, it is possible to increase muscle mass and reduce the body fat ratio. Therefore, it is possible to contribute to the prevention or improvement of sarcopenic obesity (a condition in which sarcopenia and obesity are combined).

Water is the main component of the human body, and typically accounts for approximately 60% of body weight in adult men, 55% in adult women, 70-75% in newborns and infants, and 50% in the elderly. Water ingested through drinking water or food is absorbed by the intestines and becomes "body fluids" such as blood, fulfilling the following important roles related to maintaining life: (A) to (C);
(a) Transportation: Carries oxygen and nutrients throughout the body and expels waste products from the body.
(i) Thermoregulation: Increases blood circulation to the skin and releases heat through sweating to maintain a constant body temperature.
(c) Environmental maintenance: Maintaining constant properties of body fluids to ensure smooth metabolism.

On the other hand, dehydration refers to a state in which the body is lacking in water (body fluids). Symptoms include feeling thirsty and the beginning of a decline in athletic ability when 2% of normal body fluids are lost (based on initial body weight being 100%). When 3% is lost, extreme thirst, drowsiness, and loss of appetite occur, and when it reaches 4-5%, fatigue, headaches, dizziness, etc. And when it reaches 10% or more, it can even lead to death.

The present invention can increase the proportion of water content in the body of humans and animals. Therefore, the present invention can contribute to the prevention of dehydration and the improvement of hidden dehydration, which is rarely noticed, or can contribute to health by maintaining the function of bodily fluids.

As one of the components of the body, fat plays an essential role in vital activities, such as storing energy and protecting internal organs. However, if the amount of body fat is more than the appropriate amount, it becomes obese and is a factor in causing many diseases. Traditionally, the general approach to reducing body fat has been to continually improve dietary habits to suppress energy intake and exercise habits to increase energy expenditure.

According to the present invention, the body fat percentage of humans and animals can be reduced. As shown in the examples described below, according to the present invention, the body fat percentage can be reduced without the need for any particular dietary or exercise habit modification. Therefore, even in situations where dietary or exercise habit modification is difficult, it is possible to easily reduce the body fat percentage or prevent or ameliorate obesity and various associated diseases. Alternatively, in combination with dietary or exercise habit modification, it is possible to more effectively reduce the body fat percentage or prevent or ameliorate obesity and various associated diseases.

1 is a line graph showing changes over time in muscle mass (kg), skeletal muscle mass (kg), skeletal muscle index (kg/ ^m2 ), total body water (L), body weight (kg), body fat mass (kg), and body fat percentage (%) in subjects who ingested 1-kestose. On the horizontal axis, 0W indicates before 1-kestose ingestion (week 0), 12W indicates the end of the 1-kestose ingestion period (week 12), and 52W indicates 40 weeks after the end of ingestion (week 52).

The agent for increasing muscle mass percentage, the agent for preventing or improving sarcopenia, the agent for increasing muscle mass and decreasing body fat percentage, the agent for increasing body water percentage, the agent for preventing or improving dehydration, and the agent for decreasing body fat percentage (hereinafter, these may be collectively referred to as "the agent of the present invention" or referring to any one or more of these) according to the present invention will be described in detail below.

"Muscle" refers to one or more of skeletal muscle, cardiac muscle, and smooth muscle. Also, "muscle mass percentage" refers to the percentage of muscle weight in body weight. In other words, an "increase in muscle mass percentage" means that the percentage of the body that is made up of muscle has increased.

"Percentage of body water" refers to the percentage of body weight that is made up of water (body water). In other words, "an increase in the percentage of body water" means that the percentage of water in the body has increased.

"Body fat percentage" refers to the percentage of body fat weight in body weight. In other words, "reduction in body fat percentage" means that the percentage of fat in the body has decreased.

Body weight can be easily measured using commercially available scales such as a spring balance. Muscle mass can be measured using commercially available measuring devices based on computed tomography (CT scan), magnetic resonance imaging (MRI), dual energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA). Body water and body fat can also be measured using commercially available measuring devices based on the BIA method.

Sarcopenia is a syndrome characterized by a progressive and generalized decline in skeletal muscle mass and strength. In addition to aging, causes of sarcopenia include those resulting from low activity such as being bedridden or inactive, those resulting from diseases such as severe organ failure and endocrine disorders, and those resulting from insufficient energy or protein intake due to malabsorption. Sarcopenia can lead to motor disorders, increased risk of falls and fractures, reduced ability to perform daily activities, loss of independence, and increased risk of death, so it is necessary to prevent or improve it.

Sarcopenia is diagnosed when the following conditions are met: (i) low muscle mass, (ii) low muscle strength, or (iii) low physical function (diagnostic criteria of the European Working Group on Sarcopenia in Older People (EWGSOP)). In other words, if muscle mass or skeletal muscle mass can be increased, it is believed that this can contribute to the prevention or improvement of sarcopenia. Therefore, the agent of the present invention can be used to prevent or improve sarcopenia.

As mentioned above, muscle mass can be evaluated by CT scan, MRI, DXA, or BIA. Muscle strength can be easily evaluated by measuring grip strength using a grip strength meter. Physical function can be evaluated by the Short Physical Performance Battery (SPPB) or normal walking speed (Sarcopenia: Supervised translation and Q&A of the consensus of European related academic societies on definition and diagnosis, Comprehensive research team for establishing preventive measures for age-related muscle wasting (sarcopenia) in the elderly, funded by the Ministry of Health, Labor and Welfare Science Research Grant (General Research Program on Longevity Science)).

The agent of the present invention has 1-kestose as an active ingredient. 1-kestose can be produced by carrying out an enzymatic reaction with an enzyme as disclosed in JP-A-58-201980 using sucrose as a substrate. Specifically, β-fructofuranosidase is first added to a sucrose solution, and the solution is allowed to stand at 37°C to 50°C for about 20 hours to carry out an enzymatic reaction to produce 1-kestose. The enzyme reaction solution containing the produced 1-kestose is subjected to a chromatographic separation method as disclosed in JP-A-2000-232878 to separate and purify 1-kestose from other sugars (glucose, fructose, sucrose, and oligosaccharides of 4 or more sugars). The resulting solution containing 1-kestose at high purity can be concentrated and then crystallized using a crystallization method such as that disclosed in Japanese Patent Publication No. 6-70075 to obtain 1-kestose crystals or a composition containing 1-kestose with a purity of 98% by mass or more.

In addition, since 1-kestose is contained in commercially available fructooligosaccharides, it may be used as is, or 1-kestose may be separated and purified from fructooligosaccharides by the above-mentioned method. That is, a 1-kestose-containing composition such as an oligosaccharide containing 1-kestose may be used as the 1-kestose of the present invention. When a 1-kestose-containing composition is used, the purity of the 1-kestose is preferably 80% or more, more preferably 85% or more, and even more preferably 90% or more. In the present invention, the "purity" of 1-kestose refers to the mass % of 1-kestose when the total mass of sugars is taken as 100.

The agent of the present invention can be administered orally to humans or animals, or the active ingredient can be added to an enteral nutritional agent, which can be administered by enteral nutrition via a tube inserted into the digestive tract, such as the stomach or small intestine.

The agent of the present invention can be used in the form of medicines, food additives, supplements, food compositions (drinks, seasonings, bread, confectionery, prepared foods, health foods, baby foods, other processed foods, etc.), feed, etc., in addition to those consisting only of the active ingredient 1-kestose.

When the agent of the present invention is in the form of a medicine, food additive, or supplement, the dosage form may be, for example, a solid or liquid dosage form such as a powder, tablet, sugar-coated agent, capsule, granule, dry syrup, liquid, syrup, drop, or drink. Each dosage form can be produced by a method known to those skilled in the art. For example, in the case of a powder, 800 g of 1-kestose and 200 g of lactose are thoroughly mixed, and then 300 mL of 90% ethanol is added to moisten the mixture. The moist powder is then granulated, and then air-dried at 60°C for 16 hours, and then granulated to obtain 1000 g of powder with an appropriate fineness (1-kestose content 800 mg/1 g). In addition, in the case of a tablet, 300 g of 1-kestose, 380 g of powdered reduced starch syrup, 180 g of rice starch, and 100 g of dextrin are thoroughly mixed, and then 300 mL of 90 (v/v)% ethanol is added to moisten the mixture to obtain a moist powder. This wet powder is extruded and granulated, then air-dried at 60°C for 16 hours to obtain granules. The granules are sized using an 850 μm sieve, and 50 g of sucrose fatty acid ester is added to 470 g of granules and mixed. This is compressed using a rotary tablet press (6B-2, Kikusui Seisakusho) to obtain 5,000 tablets with a diameter of 8 mm and a weight of 200 mg (1-kestose content of 60 mg per tablet).

When the agent of the present invention is in the form of a food composition, it can be produced by adding 1-kestose during the normal production process of food and beverages. 1-kestose has a sweetness index of 30, and its taste, physical properties, and processability are similar to sucrose, so various foods and beverages can be produced in the same way as sugar by replacing part or all of the sugar with 1-kestose during the production process of various foods and beverages.

When the agent of the present invention is used for humans or animals, the amount of the active ingredient to be ingested (administered) can be, for example, 0.04 g/kg body weight or more per day. The amount to be ingested is not limited to once a day, but may be divided into multiple doses.

The present invention will be described below based on each example. Note that the technical scope of the present invention is not limited to the characteristics shown in these examples. In addition, in these examples, a composition containing 1-kestose with a purity of 98% by mass or more (Butsusan Food Science Co., Ltd.) was used as "1-kestose."

The subjects (referred to as subjects 1 to 6) were six elderly men and women. The attributes of subjects 1 to 6 are shown in Table 1. All subjects had been diagnosed with sarcopenia based on the European Working Group criteria (Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010; 39(4): 412-23. doi: 10.1093/ageing/afq034. Epub 2010 Apr 13.), had an ECOG performance status of 3 (limited self-care abilities. Spend more than 50% of the day in bed or chair.; Common Toxicity Criteria, Version2.0 Publish Date April 30, 1999), had been hospitalized for a long time, and had very low activity levels.

Subjects 1 to 6 were orally administered 10 g of 1-kestose per day, twice a day, for 12 weeks. Before (week 0), after (week 12), and 40 weeks after the end of 1-kestose intake (week 52), muscle mass (kg), skeletal muscle mass (kg), skeletal muscle index (kg/m ² ), body fat mass (kg), body fat percentage (%), intracellular water (L ), extracellular water (L ), total body water (L ), and extracellular water/total body water (ECW/TBW) were measured by the BIA method using a body composition analyzer "InBody S10" (InBody Japan). Body weight (kg) was also measured at the same time. The results are shown in Figure 1. Two subjects died between weeks 12 and 52, so measurements at week 52 were performed on four subjects.

The average value and standard deviation of all subjects were calculated for the measurement results at 0 and 12 weeks, and a statistical significance test was performed to calculate the P value. The P value is shown in FIG. 1, and the average value and standard deviation are shown in Table 2. During the test period, no antibiotics or probiotics were taken. Furthermore, during the test period, relatively high-intensity exercise that would be expected to increase muscle mass or decrease body fat mass was not performed.

As shown in Table 2 and Figure 1, there was no significant difference in body weight between weeks 0 and 12. Nevertheless, intracellular water (L), extracellular water (L) and total body water were greater at week 12 than at week 0. On the other hand, there was almost no change in the extracellular water ratio between weeks 0 and 12. From these findings, it was considered that both intracellular water and extracellular water had increased to the same extent. These results demonstrated that 1-kestose increases the total body water percentage.

In addition, although there was no significant difference in body weight, muscle mass, skeletal muscle mass, and skeletal muscle index were significantly greater at 12 weeks than at 0 weeks. These results demonstrate that 1-kestose increases muscle mass percentage.

In addition, although there was no significant difference in body weight, the body fat percentage was significantly lower at 12 weeks than at 0 weeks, and the body fat mass also tended to be smaller. These results demonstrate that 1-kestose reduces the body fat percentage.

Claims (7)

A muscle mass increaser made from 1-kestose. The agent according to claim 1, which is used to prevent or improve sarcopenia. The agent according to claim 1 or 2, further characterized in that it is used to reduce body fat percentage. The agent according to claim 1, further characterized in that it is used to increase the body's water content. A body fat reduction agent whose active ingredient is 1-kestose. A method for increasing muscle mass percentage by orally ingesting 1-kestose to humans or animals (excluding medical procedures). A method for reducing body fat percentage by orally ingesting 1-kestose to humans or animals (excluding medical procedures).