JP2023125423A - Agent for promoting lipid metabolism during exercise - Google Patents

Abstract

To provide a lipid metabolism promoter that can promote lipid metabolism during exercise.SOLUTION: Provided herein is a lipid metabolism promoter including taurine, specifically a lipid metabolism promoter including taurine for use in promoting lipid metabolism during exercise. Also provided is a lipid metabolism promoter including taurine for use in promoting lipid metabolism during exercise and inhibiting carbohydrate metabolism, leading to saving of glycogen.SELECTED DRAWING: None

Description

The present invention relates to a lipid metabolism promoter during exercise.

Obesity is a risk factor for dyslipidemia, diabetes, metabolic syndrome, etc., and increases the risk of arteriosclerosis and cerebrovascular disease, so its prevention has become an urgent issue around the world.

Exercise is the most effective way to prevent and improve obesity. However, daily exercise (for example, walking, jogging) requires long periods of exercise in order to burn fat well. Furthermore, the exercise time, load intensity, etc. may be limited depending on the individual's health condition, exercise history, lifestyle, etc. Therefore, there is a need for food ingredients that can promote lipid metabolism during exercise (particularly during short-term exercise or low to moderate intensity exercise).

On the other hand, athletes who require endurance, such as marathons, bicycle road races, triathlons, skiing, and cross-country sports, become exhausted when the glycogen in their muscles is depleted. Glycogen loading, which increases glycogen stores by exercising until glycogen is depleted and then ingesting large amounts of carbohydrate food, may be performed. However, glycogen loading requires the intake of a high-carbohydrate diet, which is a burden for athletes. Therefore, there is a need for a food ingredient that can promote lipid metabolism and suppress carbohydrate metabolism during exercise (particularly during long-term exercise requiring endurance), and can ultimately lead to glycogen conservation.

Taurine (2-aminoethylsulfonic acid), which is abundantly contained in seafood such as squid and octopus, has an osmotic pressure regulating effect (Non-Patent Document 1), a bile acid secretion promoting effect, a cholesterol concentration lowering effect, and an improving effect on liver function ( Non-patent Document 2), etc., but its effects have not yet been fully elucidated.

Jean Holowach Thurston, Richard E. Hauhart, and John A. Dirgo, Life Sciences, 1980, 26(19):1561-1568 Shigeru Murakami et al., Clinical and Experimental Pharmacology and Physiology, 2016. 43(3):372-378

An object of the present invention is to provide a lipid metabolism promoter that can promote lipid metabolism during exercise.

As a result of intensive studies to solve the above problems, the present inventors found that taurine ingestion promotes lipid metabolism (particularly the use of ingested lipids as an energy source) during exercise after fat ingestion. discovered that carbohydrate metabolism was suppressed, and completed the present invention.

That is, the present invention includes the following.
[1] A lipid metabolism promoter containing taurine, which, when ingested in combination with lipids, promotes energy metabolism in a subject using the ingested lipids as an energy source during exercise.
[2] The lipid metabolism promoter according to [1], further for suppressing carbohydrate metabolism in a subject during the exercise.
[3] The subject ingests the lipid metabolism promoter once before the exercise, or repeatedly ingests the lipid metabolism promoter before the exercise or before and after the exercise, [1] or [ The lipid metabolism promoter described in [2].
[4] The lipid metabolism promoter according to any one of [1] to [3], wherein the subject ingests the lipid immediately before or during the exercise.
[5] The lipid metabolism promoter according to any one of [1] to [4], wherein the exercise is low to medium intensity exercise.
[6] The lipid metabolism promoter according to any one of [1] to [5], which suppresses increases in blood neutral fat concentration and/or blood free fatty acid concentration caused by ingested lipids.
[7] The lipid metabolism promoter according to any one of [1] to [6], wherein the subject is a subject who does not have a habit of exercising.
[8] The lipid metabolism according to any one of [1] to [7], for promoting energy metabolism in a subject using ingested lipids as an energy source during exercise of the subject by ingesting taurine in combination with lipids. Foods and drinks containing accelerators or taurine.
[9] The food or drink according to [8], further for suppressing carbohydrate metabolism in a subject during the exercise.
[10] The food or drink according to [8] or [9], further comprising a lipid.

According to the present invention, lipid metabolism during exercise can be effectively promoted.

FIG. 1 is a diagram showing the respiratory exchange ratio during exercise of a subject who was subjected to exercise after ingesting taurine and a lipid meal. FIG. 1A shows the respiratory exchange ratio during exercise in subjects who were given a single dose of taurine or a placebo, followed by a lipid meal, and were subjected to low-intensity and moderate-intensity exercise. In this single intake test, two-way analysis of variance showed that the effects of taurine and exercise intensity were significant (p<0.05, p<0.01, respectively), and the interaction was not significant (NS). FIG. 1B shows the respiratory exchange ratio during exercise in subjects who continuously ingested taurine or a placebo, then ingested a lipid meal, and performed low-intensity and moderate-intensity exercise. In Figure 1A, † (dagger mark) indicates a significant difference (p<0.05) compared to the respiratory exchange ratio during low-intensity exercise in the same intake group, as determined by a two-way analysis of variance followed by a simple main effect test. Show that there was. In Figure 1A, * (asterisk) indicates a significant difference (p<0.05) compared to the respiratory exchange ratio during exercise of the same intensity in the placebo group, as determined by a two-way analysis of variance followed by a simple main effect test. Show that. FIG. 2 is a diagram showing the amount of carbohydrate oxidation during exercise in subjects who exercised after ingesting taurine and a fat meal. FIG. 2A shows the amount of carbohydrate oxidation during exercise in subjects who ingested a single dose of taurine or a placebo, then ingested a lipid meal, and performed low-intensity and moderate-intensity exercise. In this single intake test, two-way analysis of variance showed that the effects of taurine and exercise intensity were significant (p<0.05, p<0.01, respectively), and the interaction was not significant (NS). FIG. 2B is a diagram showing the amount of carbohydrate oxidation during exercise in subjects who were subjected to continuous ingestion of taurine or a placebo, followed by ingestion of a lipid meal, and subjected to low-intensity and medium-intensity exercise. In Figure 2A, † indicates a significant difference (p<0.05) compared to the amount of carbohydrate oxidation during low-intensity exercise in the same intake group, as determined by a simple main effect test after two-way analysis of variance. shows. In Figure 2A, * indicates that there was a significant difference (p<0.05) in the amount of carbohydrate oxidation during exercise of the same intensity in the placebo group, as determined by a two-way analysis of variance followed by a simple main effect test. show. FIG. 3 is a diagram showing the amount of lipid oxidation during exercise in subjects who were given a single intake of taurine or a placebo, then a lipid meal, and subjected to low-intensity and medium-intensity exercise. Figure 4 shows blood triglyceride concentrations before and after exercise (Figure 4A) and exercise after ingesting a single dose of taurine or a placebo, then ingesting a lipid meal, and performing low-intensity and moderate-intensity exercise. The amount of increase in blood neutral fat concentration after exercise from before exercise (Δ blood neutral fat concentration) (FIG. 4B) is shown. In Figure 4A, † indicates that there was a significant difference (p<0.05) compared to the pre-exercise blood triglyceride concentration of the same intake group by a simple main effect test after two-way analysis of variance. show. Figure 5 shows the blood triglyceride concentration before and after exercise (Figure 5A), and after exercise of subjects who continuously ingested taurine or a placebo, then ingested a lipid meal, and performed low-intensity and moderate-intensity exercise. Figure 5B shows the increase in blood neutral fat concentration from before exercise (Δ blood neutral fat concentration). In this continuous intake test, two-way analysis of variance showed that the effect of taurine was not significant (NS), the effect of exercise was significant (p<0.05), and the interaction was significant (p<0.05). . In Figure 5A, † indicates that there was a significant difference (p<0.05) compared to the pre-exercise blood triglyceride concentration of the same intake group by a simple main effect test after two-way analysis of variance. show. In FIG. 5B, * indicates that there was a significant difference (p<0.05) compared to the Δ blood triglyceride concentration in the placebo group by paired t-test. FIG. 6 shows blood free fatty acid concentrations before and after exercise in subjects who continuously ingested taurine or a placebo, then ingested a lipid meal, and performed low-intensity and moderate-intensity exercise. In this continuous intake test, two-way analysis of variance showed that the effect of taurine was not significant (NS), the effect of exercise was significant (p<0.01), and the interaction was not significant (NS). In the figure, † indicates that there was a significant difference (p<0.05) compared to the pre-exercise blood free fatty acid concentration of the same intake group, as determined by a two-way analysis of variance followed by a simple main effect test. FIG. 7 shows the blood total cholesterol concentration before and after exercise in subjects who were given a single intake of taurine or a placebo, then a lipid meal, and exercised at low and moderate intensity. In this single ingestion study, two-way ANOVA results showed that the effect of taurine was not significant (NS), the effect of exercise was significant (p<0.01), and the interaction was not significant (NS). In the figure, † indicates that there was a significant difference (p<0.05) compared to the pre-exercise blood total cholesterol concentration of the same intake group, as determined by a two-way analysis of variance followed by a simple main effect test. FIG. 8 shows the blood total cholesterol concentration before and after exercise in subjects who continuously ingested taurine or a placebo, then ingested a lipid meal, and performed low-intensity and moderate-intensity exercise. In this continuous intake test, two-way analysis of variance showed that the effect of taurine was not significant (NS), the effect of exercise was significant (p<0.01), and the interaction was not significant (NS). In the figure, † indicates that there was a significant difference (p<0.05) compared to the pre-exercise blood total cholesterol concentration of the same intake group, as determined by a two-way analysis of variance followed by a simple main effect test. FIG. 9 shows blood dROMs values before and after exercise in subjects who continuously ingested taurine or a placebo, then ingested a lipid meal, and performed low-intensity and moderate-intensity exercise. In this continuous intake test, two-way ANOVA results showed a trend toward an effect of taurine (p=0.07), a significant effect of exercise (p<0.01), and a nonsignificant interaction (NS). . In the figure, † indicates that there was a significant difference (p<0.05) compared to the pre-exercise blood dROMs values of the same intake group, as determined by a simple main effect test after two-way analysis of variance. In the figure, * indicates that there was a significant difference (p<0.05) compared to the blood dROMs value at the same timing (before exercise) in the placebo group, as determined by a two-way analysis of variance followed by a simple main effect test. show.

The present invention will be explained in detail below.

The present invention relates to a taurine-containing lipid metabolism promoter, and particularly to a taurine-containing lipid metabolism promoter for promoting lipid metabolism during exercise. Specifically, the present invention relates to a lipid metabolism promoter containing taurine for promoting lipid metabolism in a subject during exercise by ingestion in combination with lipid. More specifically, the present invention relates to a lipid metabolism promoter containing taurine, which, when ingested in combination with lipid, promotes energy metabolism in a subject using the ingested lipid as an energy source during exercise of the subject.

As used herein, "taurine" refers to a substance with the chemical formula _C2H7NO3S , also _referred to as 2-aminoethanesulfonic acid or 2- _{aminoethylsulfonic} acid. Taurine may be chemically synthesized or extracted from marine products such as octopus. Taurine may be in the form of a salt, such as a sodium salt.

As shown in the examples below, when taurine is ingested in combination with lipids, it promotes lipid oxidation (lipid metabolism) during exercise after ingesting lipids, compared to when ingesting only lipids. In particular, it is possible to promote the use of ingested lipids as an energy source. Therefore, taurine has the effect of promoting lipid metabolism, particularly the effect of promoting energy metabolism in a subject using ingested lipids as an energy source during exercise, and the effectiveness of the lipid metabolism promoter of the present invention. Can be used as a component.

As shown in the examples below, when taurine is ingested in combination with lipids, it significantly reduces carbohydrate oxidation (carbohydrate metabolism) during exercise after ingesting fats, compared to when ingesting only lipids. can also be suppressed. Therefore, taurine has the effect of suppressing carbohydrate metabolism, and the lipid metabolism promoter of the present invention containing taurine can also be used to suppress carbohydrate metabolism during exercise. Therefore, the present invention provides a lipid metabolism promoter containing taurine for promoting lipid metabolism and suppressing carbohydrate metabolism during exercise. Specifically, the present invention provides a lipid metabolism promoter containing taurine that is ingested in combination with lipid to promote lipid metabolism in a subject and suppress carbohydrate metabolism in a subject during exercise. do. More specifically, the present invention provides a method for promoting energy metabolism in a subject using the ingested fat as an energy source and suppressing carbohydrate metabolism in the subject during exercise by ingestion in combination with lipid. A lipid metabolism promoter containing taurine is provided.

As used herein, "lipid metabolism" refers to the chemical conversion of lipids that takes place in the living body, as well as the transport and dynamics of lipids in the living body, including the absorption of lipids in the intestinal tract and the transfer of lipids to peripheral tissues. transport of lipids, uptake of lipids by peripheral tissues, and processes of lipid oxidation (β-oxidation) and degradation. As used herein, "lipid" is a general term for substances that are insoluble or sparingly soluble in water but soluble in organic solvents such as chloroform, such as neutral fats (triglycerides), fatty acids, cholesterol, and phosphorus. Includes lipids, etc.

In this specification, "promoting lipid metabolism" refers to promoting energy metabolism in a subject that uses ingested lipids as an energy source, for example, promoting energy metabolism in a subject that uses ingested lipids as an energy source during exercise. Includes promoting.

As used herein, "carbohydrate metabolism" refers to the chemical conversion of carbohydrates that takes place in the body, as well as the transport and dynamics of carbohydrates in the body, including the transport of carbohydrates to peripheral tissues. , the uptake of carbohydrates by peripheral tissues, and the processes of oxidation and degradation of carbohydrates by glycolysis. As used herein, "carbohydrate" is a general term for substances whose main component is sugar, and includes, for example, glucose, glycogen, and the like.

Exercise is performed by contracting muscles. Adenosine triphosphate (ATP) is used as an energy source for muscle contraction, but the amount of ATP stored in muscles is very small, so during exercise, muscles use glycolysis, aerobic systems, etc. ATP is resynthesized. In the glycolytic system, ATP is resynthesized by breaking down glycogen stored in the muscles or glucose taken from the blood. As glycolysis increases and the breakdown of glycogen and glucose progresses, lactic acid begins to accumulate. In the aerobic system, ATP is generated in the mitochondrial oxidation process of fatty acids broken down in adipose tissue, fatty acids supplied from neutral fat stored in muscles, and pyruvate synthesized in glycolysis. be resynthesized.

The contribution of the glycolytic system and the aerobic system changes depending on the intensity and duration of exercise. Specifically, the lower the exercise intensity is, the more the aerobic system is used, and the stronger the exercise intensity is, the more the glycolytic system is used. Furthermore, the longer the exercise time, the more the aerobic system is utilized.

The amount of time you can continue exercising depends on the amount of glycogen stored in your muscles, and when the glycogen stored in your muscles is used up and depleted, you become exhausted and can no longer exercise. Become. Therefore, if it is possible to conserve glycogen by promoting the use of lipids, which have a higher energy value than carbohydrates such as glycogen, as an energy source during exercise, it is possible to extend the duration of exercise.

As used herein, "energy metabolism" refers to a process in which muscle contraction and the like are performed using energy generated when ATP is converted to ADP. In this specification, "using ingested lipids as an energy source" refers to using ingested lipids directly as an energy source rather than lipids stored in the body, that is, after being ingested and absorbed, they are stored in the body. This means that ATP, which is synthesized through the oxidation and decomposition of lipids that are transported to peripheral tissues without being absorbed, is used for energy metabolism. As used herein, promoting energy metabolism that uses ingested fat as an energy source means increasing the rate of energy metabolism that uses ingested fat as an energy source, that is, promoting energy metabolism that uses ingested fat as an energy source, that is, in other words, promoting energy metabolism that uses ingested fat as an energy source This could be done by increasing the proportion of fats used directly as an energy source.

The effect of promoting lipid metabolism, particularly the effect of promoting energy metabolism in a subject using ingested lipids as an energy source during exercise, can be determined using, for example, the respiratory quotient during exercise or the amount of lipid oxidation as an index.

The respiratory quotient is the ratio of the total amount of carbon dioxide production to the total amount of oxygen consumption in the tissues of the whole body (carbon dioxide production amount/oxygen consumption amount), and represents the ratio of carbohydrate and lipid combustion (oxidation amount). The respiratory quotient is approximately 0.7 when only fats are oxidized, and 1 when only carbohydrates are oxidized. Therefore, the higher the value of the respiratory quotient, the higher the proportion of carbohydrate oxidation, and the lower the value, the higher the proportion of lipid oxidation. At rest or during exercise of a certain intensity, the respiratory quotient matches the respiratory exchange ratio (carbon dioxide output/oxygen uptake). Therefore, during exercise at a constant intensity, the respiratory exchange ratio can be measured as a respiratory quotient.

Whether or not a test substance has a lipid metabolism promoting effect can be determined, for example, by the following procedure. The test substance (e.g., taurine or the lipid metabolism promoter of the present invention) and lipid are ingested by the subject, and 60 minutes after the lipid ingestion, the subject is subjected to low-intensity and moderate-intensity exercise (e.g., bicycle rowing exercise) for 30 minutes each. The respiratory exchange ratio and lipid oxidation amount during each exercise are measured from the carbon dioxide output and oxygen intake measured during exercise. As a control, a similar operation is performed using a placebo (eg, dextrin) instead of the test substance. (i) The respiratory exchange ratio during low-intensity exercise in subjects administered the test substance is reduced compared to the respiratory exchange ratio during low-intensity exercise in subjects administered the placebo (e.g., a decrease of 1% or more). (ii) the respiratory exchange ratio during moderate-intensity exercise in subjects administered the test substance is lower than that during moderate-intensity exercise in subjects administered the test substance ( (e.g., a decrease of 1% or more), (iii) the amount of lipid oxidation during low-intensity exercise in subjects administered the test substance is compared to the amount of lipid oxidation during low-intensity exercise in subjects administered a placebo. (e.g., an increase of 1% or more, preferably 10% or more); or (iv) the amount of lipid oxidation during moderate-intensity exercise in subjects administered the test substance is greater than that in subjects administered a placebo. If the amount of lipid oxidation has increased (e.g., increased by 1% or more, preferably 10% or more) compared to the subject during moderate-intensity exercise, the test substance has a lipid metabolism promoting effect (in particular, the subject It can be determined that the drug has the effect of promoting energy metabolism in a subject using ingested fat as an energy source during exercise.

Whether or not a test substance has a carbohydrate metabolism suppressing effect can be determined, for example, by the following procedure. The test substance (e.g., taurine or the lipid metabolism promoter of the present invention) and lipid are ingested by the subject, and 60 minutes after the lipid ingestion, the subject is subjected to low-intensity and moderate-intensity exercise (e.g., bicycle rowing exercise) for 30 minutes each. The respiratory exchange ratio and the amount of carbohydrate oxidation during each exercise are measured from the carbon dioxide output and oxygen intake measured during exercise. As a control, a similar operation is performed using a placebo (eg, dextrin) instead of the test substance. (i) The respiratory exchange ratio during low-intensity exercise in subjects administered the test substance is reduced compared to the respiratory exchange ratio during low-intensity exercise in subjects administered the placebo (e.g., a decrease of 1% or more). (ii) the respiratory exchange ratio during moderate-intensity exercise in subjects administered the test substance is lower than that during moderate-intensity exercise in subjects administered the test substance ( (for example, by 1% or more), (iii) the amount of carbohydrate oxidation during low-intensity exercise in subjects administered the test substance is the same as the amount of carbohydrate oxidation during low-intensity exercise in subjects administered the placebo. or (iv) the amount of carbohydrate oxidation during moderate-intensity exercise in subjects administered the test substance is lower than that in subjects administered a placebo. If the amount of carbohydrate oxidation is lower (for example, 5% or more) compared to the amount of carbohydrate oxidation during intense exercise, it can be determined that the test substance has a carbohydrate metabolism suppressing effect.

The subject to whom the lipid metabolism promoter of the present invention is ingested is preferably a mammal or a bird. Examples of mammals include humans, primates such as monkeys, horses, cows, sheep, goats, pigs, dogs, cats, rabbits, mice, rats, etc. Primates are preferred, and primates are more preferred. is human. Examples of birds include pigeons and peregrine falcons.

In the present invention, the subject may be a subject who has a habit of exercising, such as an athlete or a racehorse, or may be a subject who does not have a habit of exercising. As used herein, the term "subject who has a habit of exercising" means a subject who has been exercising for 30 minutes or more at a time, twice or more a week, for one year or more. As used herein, a "subject who does not have a habit of exercising" means a subject who does not fall into the category of a subject who has a habit of exercising.

Generally, maximum oxygen uptake (VO ₂ max) is used as an indicator of whole body endurance. Maximal oxygen uptake (VO ₂ max) is the maximum amount of oxygen taken into the body during exercise, and the average value for a 30-year-old male is approximately 40 ml/kg/min, but the VO ₂ max of an elite long-distance athlete is known to reach up to 90ml/kg/min. In the present invention, the subject has a maximum oxygen uptake (VO ₂ max) of 20 to 90 ml/kg/min, 20 to 80 ml/kg/min, 20 to 70 ml/kg/min, and 20 to 60 ml/kg. /min, 20-50ml/kg/min, 25-45 ml/kg/min, 55-90 ml/kg/min, 55-80 ml/kg/min, 55-70 ml/kg/min, or 55- 60 ml/kg/min. The maximum oxygen uptake can be measured, for example, by subjecting the subject to a gradual exercise stress test using a bicycle ergometer, and measuring the oxygen uptake at the maximum load as VO ₂ max.

In one embodiment, the subject of the present invention has a maximum oxygen uptake (VO ₂ max) of 20 to 50 ml/kg/min, or 25 to 45 ml/kg/min, such as an average of about 35 ml/kg/min. This may be a person who does not have a habit of exercising. In one embodiment, the subject of the invention has a maximum oxygen uptake (VO ₂ max) of 55-90 ml/kg/min, 55-80 ml/kg/min, 55-70 ml/kg/min, or 55 It can be a physically active person exhibiting ~60 ml/kg/min.

In the present invention, the subject may be male or female. The subject can be, for example, a human male or a human female.

In the present invention, the subject may be a juvenile or an adult. Targets include, but are not limited to, those aged 10 to 80, 10 to 60, 10 to 40, 10 to 30, 15 to 30, 15 to 25, 20 to 25, or 20 to 22. Could be human.

In the present invention, the subject may be an obese subject or a non-obese subject. A subject without obesity can be, for example, a human having a BMI (Body Mass Index) of less than 25 (eg, a BMI of 18 or more and less than 25). Subjects who do not have obesity may also include, for example, human males with a body fat percentage of less than 20% (e.g., 4% to less than 20%, or 5% to less than 20% body fat percentage), or a body fat percentage of less than 30%. Can be a human female with a fat percentage. A subject with obesity can be, for example, a human having a BMI of 25 or more (eg, 25 or more and less than 40, 25 or more and less than 35, or 25 or more and less than 30). A subject with obesity also includes, for example, a human male with a body fat percentage of 20% or more (e.g., a body fat percentage of 20% or more and less than 40%, 20% and more than 35%, or 20% and less than 30%); or can be a human female with a body fat percentage of 30% or more.

The intake amount of the lipid metabolism promoter of the present invention can be appropriately determined in consideration of various factors such as the age and body weight of the subject. The lipid metabolism improving agent of the present invention is not limited to, for example, 10 to 1000 mg/kg body weight, 10 to 500 mg/kg body weight, 10 to 300 mg/kg body weight, 10 to 100 mg/kg body weight, 20 to 100 mg/kg per day. Body weight or 30-100 mg/kg body weight of taurine can be used to be ingested.

In the present invention, a subject may ingest the lipid metabolism promoter of the present invention before or during exercise, preferably before exercise. As used herein, "before exercise" means the time before the start of exercise. As used herein, "during exercise" means the time from the start of exercise to the end of exercise.

In the present invention, a subject may take the lipid metabolism promoter of the present invention once or repeatedly. As used herein, "repeatedly ingesting" a certain substance means ingesting the substance multiple times (ie, two or more times).

In one embodiment, the subject, for example, before exercise, e.g. within 6 hours, 5 hours, 4 hours, or 3 hours before the start of exercise, preferably 0.5 to 3 hours before the start of exercise, The lipid metabolism promoter of the present invention can be taken once 0.5 to 2 hours before exercise, 1 to 2 hours before exercise, or 1.5 hours before exercise.

In one embodiment, the subject can repeatedly ingest the lipid metabolism promoter of the present invention before exercise. For example, the target period may range from several days to several months (e.g., 3 days to 3 months, 3 days to 2 months, 3 days to 1 month, 3 to 11 days, 4 to 10 days, 5 to 9 days, Repeat the lipid metabolism promoter of the present invention, for example, 3 times a day, twice a day, once a day, every 2 days, every 3 days, or every week for 6 to 8 days or 7 days). can be ingested.

In one embodiment, the subject can repeatedly ingest the lipid metabolism promoter of the present invention before and after exercise. As used herein, repeatedly ingesting the lipid metabolism promoter of the present invention "before and after exercise" refers to ingesting the lipid metabolism promoter of the present invention at least once before exercise and at least once after exercise. It means to do. As used herein, "after exercise" means the time after the end of exercise. For example, the subject may be selected for periods ranging from before and after exercise, such as days to months (e.g., 3 days to 3 months, 3 days to 2 months, 3 days to 1 month, 3 to 11 days, 4 to 10 days, 5-9 days, 6-8 days, or 7 days), e.g., three times a day, twice a day, once a day, every two days, every three days, or every week. The lipid metabolism promoter can be taken repeatedly.

In one embodiment, the subject does not take the lipid metabolism enhancer immediately after exercise. As used herein, "immediately after exercise" means the time within 3 hours after the end of exercise.

As used herein, "exercise" means moving the body with the intention of maintaining or improving physical strength, training the body, or maintaining or improving health, and includes, but is not limited to, , sports such as marathons, bicycle road races, triathlons, skiing, cross-country, tennis, soccer, baseball, basketball, and swimming, daily exercise such as walking, jogging, cycling, stretching, yoga, and labor (e.g., agricultural work). ), housework (e.g., shopping, wiping, mopping, cleaning the bathroom, weeding the garden), and walking/cycling (e.g., commuting to work/school including walking/cycling). In the present invention, exercise is preferably low to moderate intensity exercise, such as low and/or moderate intensity exercise. As used herein, "low to moderate intensity exercise" means exercise that does not exceed the exercise intensity at the ventilation threshold (VT). The exercise intensity at the ventilatory threshold can be determined by, for example, performing an incremental exercise stress test using a bicycle ergometer and plotting the oxygen uptake (VO ₂ ) and carbon dioxide output (VCO ₂ ) measured during the test. It can be determined by specifying VT based on the V-Slope method etc. from the graph obtained. Low-intensity exercise can be, for example, exercise at 10-50%, 20-50%, 30-50% or 40% of the exercise intensity at ventilatory threshold. Moderate intensity exercise can be, for example, exercise at 50-90%, 60-80%, or 70% of the exercise intensity at ventilatory threshold. Exercise intensity can also be expressed in Mets (Metabolic equivalents), and herein, low to moderate intensity exercise is, for example, 2.0 to 8.5 Mets, 2.0 to 7.5 Mets, 2.0 to 7.0 Mets, 2.0 to 6.8 Mets, 2.0-6.5 Mets, 2.0-6.0 Mets, 2.0-5.9 Mets, 3.0-8.5 Mets, 3.0-7.5 Mets, 3.0-7.0 Mets, 3.0-6.8 Mets, 3.0-6.5 Mets, 3.0-6.0 Mets, 3.0- Exercise can be 5.9 Mets, 3.5-8.5 Mets, 3.5-7.5 Mets, 3.5-7.0 Mets, 3.5-6.8 Mets, 3.5-6.5 Mets, 3.5-6.0 Mets, or 3.5-5.9 Mets. For the Mets values of various exercises, see, for example, the "Physical Activity Standards for Health Promotion 2013" published by the Ministry of Health, Labor and Welfare (https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou /kenkou/undou/index.html). Examples of low to medium intensity exercise include walking, walking, jogging, cycling, stretching, yoga, housework, and moving by walking or cycling.

In the present invention, exercise includes, for example, 5 minutes to 10 hours, 5 minutes to 8 hours, 5 minutes to 6 hours, 5 minutes to 4 hours, 5 minutes to 2 hours, 5 minutes to 1.5 hours, 5 minutes to 1 hour. , 15 minutes to 10 hours, 15 minutes to 8 hours, 15 minutes to 6 hours, 15 minutes to 4 hours, 15 minutes to 2 hours, 15 minutes to 1.5 hours, 15 minutes to 1 hour, 25 minutes to 10 hours, 25 minutes to 8 hours, 25 minutes to 6 hours, 25 minutes to 4 hours, 25 minutes to 2 hours, 25 minutes to 1.5 hours, 25 minutes to 1 hour, 30 minutes to 10 hours, 30 minutes to 8 hours, 30 minutes to 8 hours The exercise may be performed continuously for 6 hours, 30 minutes to 4 hours, 30 minutes to 2 hours, 30 minutes to 1.5 hours, 30 minutes to 1 hour, 1 hour, or 30 minutes. Note that in this specification, even if a short break (for example, a break of about 10 seconds to several minutes) is taken during exercise, the exercise is assumed to be continued.

The lipid metabolism promoter of the present invention can exhibit its effects (lipid metabolism promoting effect, carbohydrate metabolism suppressing effect, etc.) even when a subject who does not have a habit of exercising exercises for a short time, for example. Accordingly, in one embodiment of the invention, the subject is a non-exercise subject, and the exercise is performed for 5 minutes to 1 hour, 5 minutes to 45 minutes, 5 minutes to 35 minutes, 5 minutes to 30 minutes, 15 minutes to 1 hour. time, 15 minutes to 45 minutes, 15 minutes to 35 minutes, 15 minutes to 30 minutes, 25 minutes to 1 hour, 25 minutes to 45 minutes, 25 minutes to 35 minutes, 25 minutes to 30 minutes, or continuously for 30 minutes. It can be an exercise performed.

The lipid metabolism promoter or taurine of the present invention is ingested in combination with lipids. As used herein, "ingestion of the lipid metabolism promoter or taurine of the present invention in combination with lipids" refers to intake of lipids as an energy source for energy metabolism during exercise of a subject, typically immediately before or during exercise. This means ingesting the lipid metabolism promoter of the present invention or taurine in order to utilize the lipids and promoting energy metabolism using the ingested lipids as an energy source. The lipid metabolism promoter or taurine of the present invention and the lipid are ingested so that the lipid is used as an energy source for energy metabolism during exercise of the subject, and the lipid metabolism promoter or taurine of the present invention is They may be taken at the same time or at intervals, as long as they are taken so as to promote energy metabolism using the ingested fat as an energy source.

In the present invention, lipids may be ingested in the form of foods containing lipids (e.g., foods containing a lot of fat such as meat, seafood, and nuts, processed foods, prepared foods, sweets, seasonings, and drinks). .

In the present invention, the amount of fat ingested may be, but is not limited to, a total of 5 to 50 g, 5 to 40 g, 5 to 30 g, 5 to 20 g, 5 to 15 g, or 10 to 12 g.

In the present invention, lipids may be ingested so as to be used as an energy source for energy metabolism during exercise of the subject. Accordingly, in the present invention, a subject may, for example, ingest lipids immediately before or during exercise, preferably just before exercise. As used herein, "immediately before exercise" means a time within 3 hours before the start of exercise. In the present invention, a subject may ingest fat only once immediately before and during exercise, or may ingest it multiple times (eg, 2, 3, 4, or 5 times).

In one embodiment, the subject immediately before exercise, e.g., within 3 hours before the start of exercise, 0.5-3 hours before the start of exercise, 0.5-2 hours before the start of exercise, 0.5-1.5 hours before the start of exercise, or One hour before the start, lipids can be taken (eg, just once or multiple times).

In one embodiment, the subject administers the lipids of the invention at predetermined intervals (e.g., three times a day, twice a day, once a day, etc.) over a predetermined period of time (e.g., from days to months). The metabolic enhancer can be ingested repeatedly and the fat can be ingested immediately before or during one or more exercises performed during that predetermined period.

The lipid metabolism promoter of the present invention includes additives such as carriers (solid and liquid carriers, etc.), excipients, surfactants, binders, disintegrants, lubricants, solubilizing agents, suspending agents, It may further contain a coating agent, a coloring agent, a flavoring agent, a preservative, a buffering agent, a pH adjuster), and the like.

The lipid metabolism promoter of the present invention can be used, for example, when exercising after a meal containing fat. In this case, fat ingested through meals can be efficiently used as an energy source, and obesity can be prevented. Therefore, the lipid metabolism promoter of the present invention can be used to prevent obesity.

The lipid metabolism promoter of the present invention can also suppress carbohydrate metabolism during exercise in a subject, as described above. Therefore, the lipid metabolism improving agent of the present invention can be used to suppress carbohydrate metabolism in a subject during exercise, and furthermore, to conserve glycogen during exercise. Since glycogen conservation during exercise prolongs the time until exhaustion, the lipid metabolism promoter of the present invention can also be used to extend the duration of exercise, or to improve exercise performance or endurance during exercise. It can also be used to improve strength. As used herein, "saving glycogen" refers to saving (suppressing) the consumption of glycogen stored in the body, that is, the energy source of glycogen (e.g., muscle glycogen and/or liver glycogen) in the body. In other words, it means inhibiting the decomposition of glycogen and oxidation by glycolysis.

The lipid metabolism promoter of the present invention can also suppress increases in blood neutral fat concentration and/or blood free fatty acid concentration caused by ingested lipids, as shown in the Examples below. This is thought to be due to the promotion of uptake of ingested lipids by peripheral tissues. Therefore, the lipid metabolism promoter of the present invention can be used to promote the uptake of ingested lipids by peripheral tissues (eg, muscles).

The lipid metabolism promoter of the present invention can also reduce oxidative stress, as shown in the Examples below. During exercise, oxygen consumption increases and oxidative stress increases in the body, which can contribute to aging and various diseases. Therefore, the lipid metabolism promoter of the present invention that can reduce oxidative stress can also be used to prevent conditions or diseases (eg, aging, etc.) caused by oxidative stress caused by exercise.

The lipid metabolism promoter or taurine of the present invention can be blended (added) into food and drink products. Therefore, the present invention provides the lipid metabolism promoter of the present invention or food and drink containing taurine for promoting energy metabolism in a subject using the ingested fat as an energy source during exercise by ingesting taurine in combination with lipid. We also provide products.

The lipid metabolism promoter of the present invention or the food or drink containing taurine (the food or drink of the present invention) has the same effect as the lipid metabolism promoter of the present invention. Therefore, the food and drink products of the present invention can be used for the same purpose as the lipid metabolism promoter of the present invention described above.

In the present invention, lipids and taurine may be taken in separate foods or drinks, or they may be taken in the same food or drink. Therefore, the food/beverage products of the present invention may further contain lipids.

The food and drink products of the present invention include additives that are acceptable in the production of food and drink products, such as carriers (solid and liquid carriers, etc.), excipients, surfactants, binders, disintegrants, lubricants, and solubilizing agents. It may further contain agents, suspending agents, coating agents, coloring agents, flavoring agents, preservatives, buffering agents, pH adjusting agents), and the like. The food and drink products according to the present invention may further contain water, protein, carbohydrates, vitamins, minerals, organic acids, organic bases, fruit juice, flavors, and the like.

In one embodiment, the lipid metabolism promoter or food/beverage product of the present invention may not contain caffeine and/or quercetinin. In one embodiment, the lipid metabolism promoter or food/beverage product of the present invention is not a fresh food.

The food and drink products according to the present invention may be in any form such as processed foods, prepared foods, confectionery, seasonings, supplementary foods, drinks (for example, sports drinks, jelly drinks), and the like. The food/beverage product according to the present invention may preferably be a functional food.

In the present invention, "functional food" refers to a food that can impart a predetermined functionality to living organisms, such as foods for specified health uses (including conditional FOSHU [foods for specified health uses]), foods with functional claims, and nutritional foods. Health functional foods including functional foods, special purpose foods, nutritional supplements, health supplements, supplements (e.g. tablets, coated tablets, sugar-coated tablets, capsules, liquid preparations, etc.), beauty foods (e.g. diet) It includes all kinds of health foods such as food).

The food and drink products of the present invention may be prepared in any form such as solid, liquid, mixture, suspension, paste, gel, powder, granule, capsule, etc. Furthermore, the food and drink products of the present invention may contain the lipid metabolism promoter of the present invention or taurine by any appropriate method available to those skilled in the art. Specifically, the food and drink products of the present invention may be produced by encapsulating the lipid metabolism promoter or taurine in capsules, or by wrapping the lipid metabolism promoter or taurine in an edible film, an edible coating agent, etc. Alternatively, it may be manufactured by blending (adding) a lipid metabolism promoter or taurine with an appropriate excipient, etc., and then molding it into an arbitrary form such as a tablet. The food and drink products of the present invention may be produced by processing a composition containing the lipid metabolism promoter of the present invention or taurine and other food raw materials. The food and drink products of the present invention include, for example, various foods (beverages, liquid foods, foods for the sick, nutritional foods, frozen foods, processed foods, other commercially available foods, etc.) containing a lipid metabolism promoter or taurine ( It can also be produced by adding The food/beverage products of the present invention may be produced by further containing lipids in the same manner as the lipid metabolism promoter or taurine of the present invention.

The subjects to be ingested with the food and drink products of the present invention can be set in the same manner as the subjects to be ingested with the lipid metabolism promoter of the present invention.

Hereinafter, the present invention will be explained in more detail using Examples. However, the technical scope of the present invention is not limited to these Examples.

A double-blind cross-over study was conducted with 15 healthy young men (Table 1) who do not have a habit of exercising, in which they ingested taurine or a placebo (dextrin). We investigated its influence on exercise.

<Materials and methods>
(Preparation of taurine capsules and placebo capsules)
In order to make it impossible to visually distinguish the contents, taurine (Taisho Pharmaceutical Co., Ltd., Taurine Powder 98%) and dextrin were filled into dark caramel-colored hard capsules (No. 1) to prepare taurine capsules and placebo capsules. In the single ingestion test and continuous ingestion test described below, subjects were asked to ingest seven of the above capsules (equivalent to 2 g of taurine or dextrin) per ingestion.

(Measurement of VO ₂ max and determination of VT)
Subjects underwent a progressive exercise stress test using a bicycle ergometer, oxygen uptake (VO ₂ max) at maximum load was measured, and ventilation threshold (VT) was determined based on the V-Slope method. . The test was conducted while collecting exhaled gas from the subjects using an exhaled gas analyzer (pulmonary exercise load monitoring system Aeromonitor AE-310S (Minato Medical Science), hereinafter the same).

(Single intake test)
The subjects were randomly divided into a group that received taurine (taurine group) and a group that received a placebo (placebo group). After blood was drawn from the subjects (from the elbow vein), subjects in the taurine group were given a single dose of 2g of taurine, and subjects in the placebo group were given a single dose of 2g of a placebo (dextrin). After 30 minutes, the subjects ingested a commercially available nutritional food (Calorie Mate (registered trademark) (Otsuka Pharmaceutical)) (200 kcal, 11 g of fat) as a lipid meal. 60 minutes after ingesting the fat meal (14:00-17:00), cycle for 30 minutes at a low intensity (exercise intensity of 40% of the determined VT, approximately 50 W) using a bicycle ergometer. The subjects were subjected to a rowing exercise, followed by a 30-minute bicycle rowing exercise at a moderate intensity (an exercise intensity of 70% of the determined VT, approximately 87.5 W) (50 W and 90 W on a bicycle ergometer). The exercise intensity of W corresponds to an exercise intensity of 3.5 Mets and 6.8 Mets, respectively). During exercise, subjects were fitted with an exhaled gas analyzer to measure carbon dioxide output and oxygen uptake. After completing the exercise, blood samples were taken from the subjects. The respiratory exchange ratio, the amount of lipid oxidation, and the amount of carbohydrate oxidation were calculated from the measured carbon dioxide output and oxygen intake.

Note that the amount of carbohydrate oxidation and the amount of lipid oxidation were calculated by the method described in A E Jeukendrup et al., International journal of sports medicine, 2005, 26 Suppl 1:S28-37.

Specifically, by calculating the amount of carbohydrate oxidation (g/min) per minute during each exercise using the following formula and integrating the results, the amount of carbohydrate oxidation (g/min) for 28 minutes during each exercise is calculated. /28 minutes) was calculated. (Please note that data from the first 2 minutes during each exercise cannot be measured stably, so it was not used to calculate the amount of carbohydrate oxidation (g/28 minutes). The same applies to the amount of lipid oxidation (g/28 minutes). )
Carbohydrate oxidation amount per minute (g/min) = 4.585 x minute carbon dioxide output (L/min) - 3.226 x minute oxygen uptake (L/min)

Similarly, the amount of lipid oxidation (g/min) for each minute during each exercise is calculated using the formula below, and by integrating the results, the amount of lipid oxidation (g/28 minutes) for 28 minutes during each exercise is calculated. was calculated.
Lipid oxidation per minute (g/min) = 1.695 x minute oxygen intake (L/min) - 1.701 x minute carbon dioxide output (L/min)

(Continuous intake test)
After the single-dose test, subjects in the taurine group were given 2g of taurine, and subjects in the placebo group were given 2g of a placebo three times a day (after meals) for 7 consecutive days. On the 8th day after the start of continuous intake, blood samples were taken from the subjects (from the elbow vein), and then the subjects were made to ingest a lipid meal in the same manner as in the single intake test, and subjected to bicycle rowing exercise. Blood was drawn. During exercise, subjects were fitted with an exhaled gas analyzer to measure carbon dioxide output and oxygen uptake. The respiratory exchange ratio and the amount of carbohydrate oxidation were calculated from the measured carbon dioxide output and oxygen intake using the same method as in the single intake test. After the continuous intake test, a cross-over test was conducted after a washout period (drug withdrawal period) of 10 days or more.

(Blood biochemical test)
Blood triglyceride concentration, blood free fatty acid concentration, blood total cholesterol concentration, blood insulin concentration, blood glucagon concentration, and oxidative stress level were determined from blood collected before and after exercise in single intake tests and continuous intake tests. Blood d-ROMs values) were measured. Measurements of blood neutral fat concentration, blood free fatty acid concentration, and blood total cholesterol concentration were carried out outsourced to SRL Co., Ltd. Blood insulin concentration was measured using Mercodia human insulin ELISA kit (Funakoshi). Blood glucagon concentration was measured using Glucagon EIA kit (YK090) (Yanaihara Institute). The degree of oxidative stress was measured using a free radical analyzer Free Carrio Duo (WISMERLL). Data were analyzed by two-way analysis of variance.

<Results>
The average VO ₂ max (ml/kg/min) of the 15 subjects was 35.1±1.2 (26.1-44.4).

In the single intake test and the continuous intake test, the respiratory exchange ratio during exercise in the taurine group was lower than that in the placebo group at both low and moderate exercise intensities (FIGS. 1A and B). Furthermore, as a result of a two-way analysis of variance using taurine intake and exercise intensity as factors for the respiratory exchange ratio in the single ingestion test, the interaction was not significant, and the effects of taurine and exercise intensity were significant (respectively, p<0.05, p<0.01) (Fig. 1A).

In a single intake test and a continuous intake test, the amount of carbohydrate oxidation during exercise in the taurine group was lower than that in the placebo group at both low and moderate exercise intensities (FIGS. 2A and B). Furthermore, regarding the amount of carbohydrate oxidation in the single intake test, a two-way analysis of variance using taurine intake and exercise intensity as factors revealed that the interaction was not significant, and the effects of taurine and exercise intensity were significant (each , p<0.05, p<0.01) (Fig. 2A).

In a single intake test, the amount of lipid oxidation during exercise in the taurine group was increased compared to the placebo group at both low and moderate exercise intensities (Figure 3).

These results showed that taurine intake suppresses carbohydrate oxidation (metabolism) and promotes lipid oxidation (metabolism) during exercise after fat ingestion.

In the single intake test and the continuous intake test, the blood triglyceride concentration after exercise was significantly increased in the placebo group compared to before exercise, but the blood triglyceride concentration was significantly increased in the taurine group. (Figures 4 and 5).

Similarly, in the continuous intake test, the blood free fatty acid concentration after exercise was significantly increased in the placebo group compared to before exercise, but no significant increase in blood free fatty acid concentration was observed in the taurine group. (Figure 6).

In this study, because the lipids ingested before exercise were absorbed and transported into the blood by chylomicrons, an increase in blood neutral fat concentration and blood free fatty acid concentration was observed after exercise in the placebo group. It is thought that the In contrast, in the taurine group, the uptake by peripheral tissues of neutral fats and free fatty acids that were absorbed and transported into the blood was promoted, resulting in lower blood neutral fat concentrations and blood free fatty acids after such exercise. It is considered that no increase in concentration was observed.

Therefore, the result that taurine suppressed the increase in blood triglyceride concentration and blood free fatty acid concentration after exercise suggests that taurine intake promotes the uptake of ingested lipids by peripheral tissues. It was shown that the proportion of ingested lipids used directly as an energy source, rather than stored lipids, was increased.

In both the single intake test and the continuous intake test, no effect of taurine intake was observed on blood total cholesterol (Figures 7 and 8). Since blood cholesterol is present in lipoproteins, taurine intake is not thought to affect the amount of lipoproteins that transport triglycerides.

In both single and continuous intake tests, no effect of taurine intake was observed on blood insulin levels and blood glucagon levels.

In a continuous intake test, pre-exercise blood d-ROMs (Diacron-Reactive Oxygen Metabolites) values (indicating the degree of oxidative stress) in the taurine group were significantly lower than pre-exercise blood d-ROMs values in the placebo group. Ta. This demonstrated that taurine ingestion had an effect of reducing oxidative stress (Figure 9).

Claims (10)

A lipid metabolism promoter containing taurine, which is used in combination with lipids to promote energy metabolism in a subject using the ingested lipids as an energy source during exercise. The lipid metabolism promoter according to claim 1, further for suppressing carbohydrate metabolism in a subject during the exercise. 3. The subject ingests the lipid metabolism promoter once before the exercise, or repeatedly ingests the lipid metabolism promoter before the exercise or before and after the exercise. Lipid metabolism promoter. The lipid metabolism promoter according to any one of claims 1 to 3, wherein the subject ingests the lipid immediately before or during the exercise. The lipid metabolism promoter according to any one of claims 1 to 4, wherein the exercise is low to medium intensity exercise. The lipid metabolism promoter according to any one of claims 1 to 5, which suppresses increases in blood neutral fat concentration and/or blood free fatty acid concentration caused by ingested lipids. The lipid metabolism promoter according to any one of claims 1 to 6, wherein the subject is a subject who does not have a habit of exercising. The lipid metabolism promoter according to any one of claims 1 to 7, for promoting energy metabolism in a subject using the ingested lipid as an energy source during exercise of the subject by ingesting taurine in combination with a lipid; Foods and drinks containing taurine. The food or drink according to claim 8, further for suppressing carbohydrate metabolism in a subject during the exercise. The food/beverage product according to claim 8 or 9, further comprising a lipid.

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