JPH11239464A - Composition capable of removing risk factors during exercise - Google Patents

Abstract

(57) [Problem] To provide a composition having a function of removing a risk factor at the time of exercise which can be used in the fields of a health food for preventing sports anemia, a health food for preventing a risk such as sudden death during exercise, and a preventive medicine. Offer. SOLUTION: The composition having an ability to remove a risk factor during exercise characterized by containing an n-3 polyunsaturated fatty acid as an active ingredient. The ability to remove risk factors during exercise is, for example, the ability to prevent sports anemia. The n-3 highly unsaturated fatty acid is an n-3 highly unsaturated fatty acid or / and a derivative thereof. The n-3 polyunsaturated fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid. The n-3 polyunsaturated fatty acids are preferably in the form of natural triglycerides such as fish oil. The composition having the ability to remove risk factors during exercise according to the present invention is suitable as a food composition, particularly a sports food. Alternatively, it can be used as a pharmaceutical composition.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition having an ability to remove a risk factor during exercise, which can be used in the fields of food, prevention and medicine.

[0002]

2. Description of the Related Art Exercise is encouraged because exercise facilitates metabolism in the body and eliminates risk factors for adult diseases. Medically, there are considerable reports on exercise effects as rehabilitation for patients with myocardial infarction. However, on the other hand, various diseases and complications during sports have become problems in sports medicine, and one of them is "sports anemia" and "sudden death". The causes of sports anemia include physical deficiencies such as increased erythrocyte production due to increased protein metabolism and insufficient intake of iron during exercise, hemolysis by lactic acid and other chemicals produced during exercise, and shock during exercise. Hemolysis by action is considered. Sudden death often has a chronic underlying disease, but some of the underlying morphological diseases are unclear, and it is often difficult to make a definitive diagnosis.
There have been many reports of sudden deaths during sports, but there are overwhelmingly many running types such as running, jogging, marathon, etc.
Many died suddenly during baseball and swimming.

[0003] As described above, most of the endogenous deaths that suddenly died during sports are acute cardiac deaths, and most of them have no abnormalities, either subjectively or objectively. In the rest, there were no subjective abnormalities, and in many cases, even if a heart disease was suspected, a close examination determined that there was no abnormality, and only a few cases were treated. Of course, in a sudden death case diagnosed as having acute cardiac dysfunction, it is natural that he lived as a healthy person and did not receive medical care before his birth.

[0004] In general, in the case of sudden death, there are cases in which a latent basic organic disease is recognized, cases in which the basic organic change is mild, or cases in which no obvious organic change is recognized, and in the former case, There are few problems because there are subjective symptoms and some people are receiving medical care. However, in the latter case, the individual lacks subjective symptoms, and even if a physical examination is taken, it is determined that there is no abnormality, and then sudden death due to sports or other activities causes social problems. Acute heart failure of unknown origin in young people (so-called Pockli's disease) belongs to the latter and is often a problem associated with extreme exercise or ironing.

[0005] The nature of acute heart failure in young people is still unknown and there are various theories. In general, seemingly healthy and physique-healthy young men (overwhelmingly male) have a sudden growl. And suddenly die. At necropsy, mild cardiac hypertrophy accompanied by dilatation of the heart and thinning and narrowing of the vascular system such as the coronary arteries and aorta are observed, but there is almost no arteriosclerosis. It is necessary to consider the possibility of arrhythmia and sudden death during and after exercise.

[0006] Sawaki et al. Of Juntendo University noted that Norwegian athletes who performed well at the Lillehammer Winter Olympics used DHA and EPA as dietary supplements, The effect of ingestion on the training effect was studied. As a result, there was a big difference in their performance, DHA, EP
It is speculated that ingestion of A causes an improvement in the ability to transport oxygen to capillaries. In the future, studies on the effects of these fatty acids on motor function are expected to become more active.On the other hand, the relationship between decreased erythrocyte deformability and erythrocyte membrane stiffness has been reported in several diseases, It is considered that the increase in the fluidity of erythrocyte may cause the fragility of red blood cells, and development of a risk factor elimination agent for exercise that can be used in the fields of prevention and medical care based on these findings is awaited.

[0007]

An object of the present invention is to provide a health food for preventing sports anemia, etc., a health food for preventing the risk of sudden death during exercise, and a risk factor for exercise which can be used in the fields of preventive medicine. An object of the present invention is to provide a composition having a removing ability. An object of the present invention is to provide a composition having the ability to remove a risk factor during exercise for healthy persons such as sports professionals, athletes, sports enthusiasts, those who want to play sports, and those who aim to improve endurance. It is to provide as a food or a pharmaceutical composition.

[0008]

SUMMARY OF THE INVENTION It is believed that changes in blood rheology during exercise may cause sudden death. The present inventors have made a working hypothesis that “marine foods may improve blood viscosity”, and epidemiological studies targeting fishermen with high fish meat intake and farmers with relatively low fish meat intake compared to fishermen. Investigations, fish oil concentrates, highly purified eicosapentaenoic acid ethyl ester (EPA / EE) based, clinical experiments have already shown that EPA contained in fish oil components improves blood viscosity. Subsequently, the mechanism of action of EPA has been studied mainly for the erythrocyte membrane from the viewpoint of hemorheology. The present inventors have found for the first time that n-3 polyunsaturated fatty acids not only act on normal blood rheology but also suppress undesired changes in blood rheology due to exercise. It has made it possible to provide health foods to prevent, health foods to prevent risks such as sudden death during exercise, and preventive medicines.

[0009] The gist of the present invention is a composition having an ability to remove a risk factor during exercise characterized by containing an n-3 polyunsaturated fatty acid as an active ingredient. The above n-3
The highly unsaturated fatty acid is an n-3 highly unsaturated fatty acid or a derivative thereof. The n-3 polyunsaturated fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid. The n-3 polyunsaturated fatty acids are preferably in the form of natural triglycerides such as fish oil.
The composition having the ability to remove risk factors during exercise according to the present invention is suitable as a food composition, particularly a sports food. Alternatively, it can be used as a pharmaceutical composition.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, as the n-3 polyunsaturated fatty acid, an n-3 polyunsaturated fatty acid or / and a derivative thereof is used. Free fatty acids and or glyceride esters for food compositions, free fatty acids for pharmaceutical compositions, pharmaceutically acceptable salts thereof,
Use esters or amides.

More specifically, for example, n-type highly unsaturated fatty acids such as refined fish oil and oils and fats with enhanced absorbency such that 60% or more of the remaining fatty acids of the constituent fatty acids are medium-chain fatty acids. A fat or oil composition containing a -3 type highly unsaturated fatty acid as a main component, or a mixture of any fatty acid or ester thereof obtained from a natural fat or oil containing a large amount of derivatives such as eicosapentaenoic acid or glyceride thereof can be used. A mixture of fatty acids or esters obtained from appropriate fish such as fish such as sardine, mackerel, herring, saury, animal marine plankton such as antarctic krill, tsunonashi krill, and copepoda can be used.

The purification of fish oil is performed to remove these from crude oil containing free fatty acids, odor components, coloring components, and the like collected from the raw materials. The refining methods include alkali refining, steam blowing, There are adsorption methods and the like, which are performed in any combination. The alkali purification method is also called a deoxidation method,
In this method, sodium hydroxide is added to the crude oil to convert the free fatty acids in the fish oil into foots (soaps), and impurities are adsorbed or dissolved in the foots to remove the impurities, thereby purifying the crude oil. The steam blowing method is a method in which a refined oil is heated to about 150 ° C. under reduced pressure, and steam is blown into this to remove odor components. The adsorption method is a method of adsorbing and removing coloring components and odor components in crude oil using an adsorbent such as activated carbon and acid clay.

By making full use of these known purification methods, fish oil is purified to tasteless and odorless and used. Furthermore, cholesterol can be substantially removed from fish oil to prepare a tasteless and odorless fish oil having a cholesterol content of 0.1% or less and a high content of EPA and DHA. Fatty acids such as EPA and DHA contained in tasteless and odorless fish oil exist in the form of triglycerides. The content of EPA and DHA is, for example, EPA 18%, DHA 8 to 12%, EPA 2
8%, DHA12%, EPA5-8%, DHA2
It can be arbitrarily changed according to the intended use such as 2%.

The above-mentioned high-purity EPA and its ester are obtained by subjecting a mixture of fatty acids or their esters obtained from natural fats and oils containing eicosapentaenoic acid and / or a derivative thereof to precise distillation under high vacuum by a plurality of distillation towers.
To obtain a fraction containing a fatty acid or an ester thereof as a main component, and then fractionate and purify the fraction by column chromatography in a reversed-phase partition system. High purity DH
A and its ester can be obtained by almost the same operation.

The composition of the present invention having the ability to remove risk factors during exercise can be used in the fields of health foods for preventing the risk of sudden death during exercise, health foods for preventing sports anemia, etc., and preventive medicines. Are suitable. It is possible to use a composition having the ability to remove risk factors during exercise for healthy people such as sports professionals, athletes, sports enthusiasts, those who want to play sports, those who aim to improve endurance as sports foods. it can. It can also be used as a pharmaceutical composition.

[0016] In the health food of the present invention for preventing the risk of sudden death during exercise, etc., in addition to the essential n-3 polyunsaturated fatty acids, vitamins usually added to foods as optional components , Carbohydrates, pigments, fragrances and the like can be appropriately compounded. Further, an emulsifier can be added as needed. Examples of the emulsifier include glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, soybean phospholipid, and propylene glycol fatty acid ester, and these may be used alone or in combination. The food can be eaten in any form, liquid or solid. It can be eaten as a soft capsule encapsulated by encapsulation with gelatin or the like. Capsules are made of, for example, a gelatin film prepared by dissolving raw gelatin in water by adding water and adding a plasticizer (glycerin, D-sorbitol, or the like) thereto.

The above composition can be used as an agent for removing a risk factor during exercise comprising an n-3 polyunsaturated fatty acid or a pharmaceutically acceptable salt, ester or amide thereof as an active ingredient. The n-3 type polyunsaturated fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid, and is used not only as the acid itself but also as a pharmaceutically acceptable salt, ester or amide thereof. As the drug, n-3 polyunsaturated fatty acid can be used alone as a preparation, or a pharmaceutical composition prepared by adding a pharmaceutically usable carrier or diluent can be used. Such formulations or pharmaceutical compositions can be administered by the oral or parenteral route.
For example, solid or fluid (gel and liquid) formulations or pharmaceutical compositions for oral administration may take the form of tablets, capsules, tablets, pills, powders, granules or gel preparations. The precise dosage of the formulation or pharmaceutical composition will depend on the intended use and the duration of the treatment, and will be such that the attending physician or veterinarian would consider appropriate. It is clear that a preparation or a pharmaceutical composition which is an agent for removing a risk factor at the time of exercising comprising an n-3 polyunsaturated fatty acid as an active ingredient may be combined with administration with other pharmacologically active substances.

[0018]

[Effects] As factors affecting blood viscosity, there are various factors such as erythrocyte deformability, hematocrit value, and plasma viscosity, and these factors seem to affect each other and change the viscosity. In the case of EPA, it is considered to be due to improving the deformability of red blood cells. The erythrocyte deformability is determined by the surface area / volume ratio of blood cells, erythrocyte internal viscosity,
It is determined by the viscoelasticity of the film. When healthy fish were administered purified fish oil for 10 weeks, no change was observed in the hematocrit value of the fish oil intake group and the non-administration group, but a significant increase in erythrocyte deformability was observed in the fish oil intake group, The increase in yield value observed in the intake group was not observed in the fish oil intake group.

[0019]

EXAMPLES The present invention will be described below with reference to specific examples, but the present invention is not limited by these examples.

Reference Example 1 << Effect on Normal Blood Rheology >> Eicosapentaenoic acid (EP
AC _{20: 5} , n-3)] Red blood cell Fragility (deformability)
<Summary> By administering EPA / EE 3.6 g / day for 4 weeks, the erythrocyte hemolysis start value, maximum hemolysis value, and hemolysis end value significantly shift to the lower osmotic pressure side as compared to before administration, and the erythrocyte membrane Strengthening was suggested. It is significant that the increase in erythrocyte deformability and membrane strengthening were simultaneously measured as in this experiment,
In addition to the safety of administration, it was considered that blood vessel walls and somatic cells became flexible and highly safe cells.

<< Purpose >> As factors affecting blood viscosity, there are various factors such as erythrocyte deformability, hematocrit value, plasma viscosity, and these factors are considered to affect each other and change the viscosity. In the case of EPA, it is considered to be due to improving the deformability of red blood cells. Erythrocyte deformability is determined by the surface area / volume ratio of blood cells, erythrocyte internal viscosity, viscoelasticity of the membrane, and the like. EPA
In the case of, it is considered to be due to the fluidity of the membrane. blood,
In particular, the erythrocytes can be provided with flexibility so that the size of the erythrocytes can be transformed into a shape that allows the erythrocytes to smoothly pass through the capillaries. On the other hand, the relationship between reduced erythrocyte deformability and erythrocyte membrane stiffness has been reported in several diseases, and an increase in erythrocyte membrane fluidity may be at risk of erythrocyte weakness. Therefore, in this experiment, EPA / EE was administered to healthy individuals for 4 weeks, and the effect of EPA on erythrocyte fragility was examined using the Coil Planet Centrifug.
It examined by the e method. This method is a method of measuring osmotic resistance of red blood cell membrane developed by Kimura et al.

<< Method >> EPA purified from sardine edible part
-EE 3.6 g / day, 10 healthy subjects (average age 36
Aged) for 4 weeks. Blood collection was performed according to the method of Reid's et al. That is, 0.5 ml of blood is 30
5 μm nucleopore me under water pressure of 5 cm
measuring the time passing Mbranefilter, amount blood cells passing through the hematocrit value to 30 seconds (V _RBC m
1/30 sec) and used as an index of erythrocyte deformability. Statistical processing is performed by the student t-test (pair
Using d), the significance level was a two-sided risk ratio of 5%.

<Results> EPA / EE was reduced to 1 in 10 healthy persons.
By administering 3.6 g per day for 4 weeks, E in the erythrocyte membrane
PA content ranges from 2.01 ± 0.35 mol% to 4.00.
Increased to ± 0.34 mol%. Table 1 shows the measurement results of the hemorheological factors. Blood viscosity yield value (shear
rate) (low rotation) = 37.5 sec ^-1 is significant (P <0.
01), yield rate (shear rate) (rotational height) = 3
75 sec ^-1 also showed a significant (P <0.001) decrease. Erythrocyte deformability was significantly (P <0.05) increased, and plasma viscosity was significantly (P <0.05) decreased. Erythrocyte Osmotic Resistance Measurement Results (A) (B)
(C) is shown in FIGS. (A) The osmotic pressure of red blood cells at the start of hemolysis
0.7 ± 3.13 mOsm) after administration (96.5 ± 2.4).
(2 mOsm), (B) The osmotic pressure of red blood cells at the time of maximum hemolysis is from 86.1 ± 2.18 mOsm before administration (82.6 ± 21.8 ± Osm).
2.32 mOsm), (C) The osmotic pressure of red blood cells at the end of hemolysis is from before (69.4 ± 2.76 mOsm) to after (6.
9.4 ± 2.76 mOsm) (P <0.0
1).

[0024]

[Table 1]

<Consideration> In this experiment, the EPA content in the erythrocyte membrane was 2.01 ± 0.35 mol% to 4.00 ± 0.
The increase was about 2 times as high as 34 mol%, and a significant decrease in blood viscosity and a significant increase in erythrocyte deformability were observed. Lipids in the erythrocyte membrane are free cholesterol (FC), phosphat
idyl ethanolamine (PE), phospharidyl serine (P
S), phosphataidylcholine (PC) and sphingmyel
There is in (SM), PE and PS are abundant in the inner layer of lipid bilayer, PC and SM are mainly distributed in the outer layer, and FC is uniformly present in the inner and outer layers. Of these, PC imparts fluidity to the membrane, while FC and SM increase viscosity and stiffen the membrane. SM is said to be more powerful than FC in stiffening the membrane. In a report by Tamura et al. Administered EPA / EE3.6 g / day, the measurement of arachidonic acid (AA) and EPA content in each platelet phospholipid fraction showed that AA in PC and PE was measured.
Content was significantly reduced, and EPA was reported to have increased in PC, PE, PI and PS, and was likely in erythrocytes as well. In particular, P, which increases the fluidity of the membrane
The decrease in AA and the increase in EPA in C are interesting. The fact that EPA having the lowest viscosity among fatty acids is particularly increased in PC in the membrane suggests a relationship between the EPA content and the fluidity of the membrane, but may be at risk of weakening of the membrane. EP of this experiment
Administration of 3.6 g / day of A.EE for 4 weeks significantly shifted the erythrocyte hemolysis start value, maximum hemolysis value, and hemolysis end value to the osmotic side as compared to before administration, suggesting enhancement of the erythrocyte membrane. . It is significant that the increase in erythrocyte deformability and membrane strengthening were simultaneously measured in this experiment, and it is thought that not only the safety of administration but also that blood vessel walls and somatic cells become flexible and highly safe cells. Was done.

Example 1 << Effects on Changes in Blood Rheology During Exercise >> Dosage / use formulation 1) 1.6 g / day of EPA is ingested. 2) Take refined fish oil capsules containing 28% EPA and 12% DHA, 300 mg x 18 tablets / day, 9 tablets immediately after meal in the morning and evening. 2. 2. Number of subjects 1) 1 group, 6 persons x 2 groups [EPA administration group (Fish), EPA non-administration group (non-fish)] Test Method 1) The EPA administration group ingests 18 refined fish oil capsules / day from 10 weeks before entering high altitude training to the end of high altitude training according to the schedule shown in Table 2. 2) In each group, at the start of administration, at the start of high altitude training,
At the end of the high altitude training, the following items shall be measured.

[0027]

[Table 2]

4. Measurement items 1) Biochemical items Measurement items (a) Fatty acid composition (plasma, erythrocyte membrane phospholipid) (b) Erythrocyte deformability (c) Yield value (d) Amino acid composition 2) Physiological item (exercise ability) (1) ) Measurement items (a) Maximum oxygen uptake (b) MSS (Maximum Steady Sta
te) Measurement: Change and improvement of endurance in the EPA administration / non-administration group were examined. Blood at rest is collected before and after each workout and analyzed for the items described above. After running at two different speeds before and after each training, the blood lactate concentration is measured to determine a running speed equivalent to 4 mmol / l (MSS). Using this MSS as an index, we will consider improving endurance.

<Results> As shown in FIGS. 4 to 9 and Tables 3 and 4, no change was observed in the hematocrit value in the fish oil intake group and the non-fish intake group. A significant increase was observed, and the increase in whole blood viscosity observed in the fish oil non-administration group was not observed in the fish oil intake group.

[0030]

[Table 3]

[0031]

[Table 4]

[0032]

The present invention provides a health food that prevents sports anemia, a health food that prevents the risk of sudden death during exercise, and a composition having the ability to remove risk factors during exercise that can be used in the fields of preventive medicine. Can be. Sports professionals,
Athletes, sports enthusiasts, those who want to play sports,
A composition having an ability to remove a risk factor during exercise for a healthy person such as a person aiming at improving endurance can be provided as a food for sports in particular.

[Brief description of the drawings]

FIG. 1 is a drawing showing the effect of EPA-EE administration for 4 weeks on erythrocyte osmotic pressure (at the start of hemolysis) in healthy subjects.
The vertical axis of the graph is the osmotic pressure of red blood cells.

FIG. 2 is a graph showing the effect of EPA-EE administration for 4 weeks on erythrocyte membrane osmotic pressure (at the time of maximum hemolysis) in healthy subjects.

FIG. 3 is a graph showing the effect of administration of EPA-EE for 4 weeks on erythrocyte osmotic pressure (at the end of hemolysis) in healthy subjects.

FIG. 4 is a graph showing changes in erythrocyte deformability of healthy individuals after administration of EPA-containing purified fish oil for 10 weeks.

FIG. 5 is a graph showing changes in the yield value of healthy fish after administration of EPA-containing purified fish oil for 10 weeks.

FIG. 6 is a graph showing changes in the yield value of a healthy subject after administration of EPA-containing purified fish oil for 10 weeks.

FIG. 7 is a graph showing a change in hematocrit value of healthy fish after administration of EPA-containing purified fish oil for 10 weeks.

FIG. 8 is a drawing showing changes in the erythrocyte fatty acid composition of the fish oil intake group.

FIG. 9 is a graph showing changes in the erythrocyte fatty acid composition of a control group.

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[Procedure amendment]

[Submission date] September 4, 1998

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0023

[Correction method] Change

[Correction contents]

<Results> EPA / EE was reduced to 1 in 10 healthy persons.
By administering 3.6 g per day for 4 weeks, E in the erythrocyte membrane
PA content ranges from 2.01 ± 0.35 mol% to 4.00.
Increased to ± 0.34 mol%. Table 1 shows the measurement results of the hemorheological factors. Blood viscosity yield value (shear
rate) (low rotation) = 37.5 sec ^-1 is significant (P <0.
01), yield rate (shear rate) (rotational height) = 3
75 sec ^-1 also showed a significant (P <0.001) decrease. Erythrocyte deformability was significantly (P <0.05) increased, and plasma viscosity was significantly (P <0.05) decreased. Erythrocyte Osmotic Resistance Measurement Results (A) (B)
(C) is shown in FIGS. (A) The osmotic pressure of red blood cells at the start of hemolysis
0.7 ± 3.13 mOsm) after administration (96.5 ± 2.4).
(2 mOsm), (B) The osmotic pressure of red blood cells at the time of maximum hemolysis is from 86.1 ± 2.18 mOsm before administration (82.6 ± 21.8 ± Osm).
2.32 mOsm), (C) The osmotic pressure of erythrocytes at the end of hemolysis is from before (69.4 ± 2.76 mOsm) to after ( 6 ).
6.0 ± 3.33 mOsm) (P <0.0
1).

Claims (10)

[Claims] 1. A composition having the ability to remove risk factors during exercise, comprising an n-3 polyunsaturated fatty acid as an active ingredient. 2. The composition having the ability to remove risk factors during exercise according to claim 1, wherein the ability to remove risk factors during exercise is an ability to prevent sports anemia. 3. The composition according to claim 1, wherein the n-3 polyunsaturated fatty acid is an n-3 unsaturated fatty acid and / or a derivative thereof. 4. The composition according to claim 1, wherein the n-3 polyunsaturated fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid. 5. The composition according to claim 1, wherein the n-3 polyunsaturated fatty acid is in the form of natural triglyceride. 6. The composition according to claim 5, wherein the n-3 polyunsaturated fatty acid is fish oil. 7. The composition according to claim 1, wherein the composition is a food composition. 8. The composition according to claim 7, which is a sports food and has the ability to remove risk factors during exercise. 9. The composition according to claim 1, wherein said composition is a pharmaceutical composition. 10. The composition capable of removing a risk factor during exercise according to claim 9, wherein the derivative of the n-3 polyunsaturated fatty acid is a pharmaceutically acceptable salt, ester or amide.