JP2020016651A - Index value determination system, mitochondrial activity evaluation system, index value determination method, and mitochondrial activity evaluation method - Google Patents

Abstract

To provide an index value determination system capable of determining an index value that makes it easier to comprehend mitochondrial activity.SOLUTION: The index value determination system includes: a density value acquisition unit 2 that continuously or intermittently acquires the concentration of acetone released from a subject who has ingested at least one selected from acetone-producing species 3-hydroxybutyrate, 3-hydroxybutyrate, 3-hydroxybutyrate, and acetoacetic acid, which are finally decomposed in the body to produce acetone; and an index value output unit 3 that determines an index value having a correlation with the mitochondrial activity of the subject using at least the acquired acetone concentration value.SELECTED DRAWING: Figure 1

Description

  The present invention provides an index value determining system and an index value determining method for determining an index value having a correlation with a subject's mitochondrial activity, and a mitochondrial activity evaluating system and a mitochondrial activity evaluating method for evaluating mitochondrial activity based on the index value. About.

  Mitochondria are important organs that produce energy inside cells, and have the function of converting ingested nutrients to ATP (adenosine triphosphate), which is an energy storage substance. Mitochondrial activity gradually decreases due to aging and the like. Recent studies have revealed that when the mitochondrial activity decreases, more active oxygen is generated, which causes aging and various diseases. Therefore, grasping mitochondrial activity contributes to prevention of aging and lifestyle-related diseases.

  Conventionally, as a method for measuring mitochondrial activity, for example, a method for measuring mitochondrial metabolic activity disclosed in Patent Document 1 has been proposed. This method for measuring the metabolic activity of mitochondria is performed by using cells collected from a living body such as a mammal or cultured cells, subjecting the cells to a permeation treatment using a streptolysin-O-containing solution, and treating the mitochondria of the permeated cells. This is a method for measuring the energy metabolic activity of a plant. According to this method for measuring mitochondrial metabolic activity, metabolic activity can be measured without damaging the mitochondrial membrane.

JP 2011-205935 A

  Here, from the viewpoint that grasping mitochondrial activity contributes to prevention of aging and lifestyle-related diseases, for example, it can be measured as one of the examination items of a health examination, or the subject can measure it on a daily basis. It is important that mitochondrial activity can be easily measured without complicated work and can be easily grasped.

  However, in the method for measuring the metabolic activity of mitochondria described in Patent Document 1, it is necessary to use cells taken out of the body, so that the measurement operation must be complicated, and mitochondrial activity cannot be easily measured. Therefore, mitochondrial activity cannot be easily grasped.

  The present invention has been made in view of the above circumstances, an index value determination system and an index value determination method capable of determining an index value that enables easy understanding of mitochondrial activity, and mitochondria based on the index value. It is an object of the present invention to provide a mitochondrial activity evaluation system and a mitochondrial activity evaluation method capable of easily evaluating the activity.

  Therefore, in order to achieve the above object, the present inventor has conducted intensive studies on a method capable of easily grasping mitochondrial activity, and as a result, the correlation between the concentration of acetone released outside the body and the mitochondrial activity was determined. Focusing on the property, it was found that mitochondrial activity can be grasped by determining an index value having a correlation with mitochondrial activity based on the concentration value of acetone, and further that mitochondrial activity can be evaluated using this index value. Was.

  In other words, when carbohydrate restriction or the like is performed, the amount of sugar in the body becomes insufficient. Therefore, fat in the body is decomposed to produce a ketone body, and the ketone body is used to generate energy in mitochondria. Specifically, fatty acids produced by the decomposition of fat are decomposed in mitochondria to 3-hydroxybutyric acid, which is oxidized to acetoacetic acid. Then, acetoacetic acid is taken into the TCA circuit (citric acid circuit) via acetoacetyl-CoA and used as energy.

  At this time, if there is not enough mitochondrial activity to consume the supplied acetoacetic acid as the fat is decomposed, the consumption of the supplied acetoacetic acid cannot catch up, and the acetoacetic acid is decomposed into acetone and carbon dioxide, and mitochondria Acetone emitted from body fluids is released together with exhalation or evaporates from the skin, so that the body emits acetone odor.

  In other words, when mitochondrial activity is high, the consumption of acetoacetic acid in the body increases, so the concentration value of acetone released outside the body decreases, and conversely, when mitochondrial activity is low, the consumption of acetoacetic acid decreases Therefore, the concentration value of acetone released outside the body increases. Thus, since there is a correlation between the concentration of acetone released outside the body and mitochondrial activity, the amount of ketone bodies in the body is intentionally increased to reduce the amount of acetone generated from the subject. If detected, mitochondrial activity can be grasped by determining an index value having a correlation with mitochondrial activity based on the acetone concentration value, and mitochondrial activity can be evaluated based on this index value.

That is, the characteristic configuration of the index value determination system according to the present invention is:
A subject who has ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate, and acetoacetic acid, which are acetone-producing species that are finally decomposed in the body to generate acetone. Concentration value acquisition means for continuously or intermittently acquiring the concentration value of the acetone released from the
An index value determining means for determining an index value having a correlation with the mitochondrial activity of the subject using at least the acquired acetone concentration value.
Further, using the index value determination system, the characteristic configuration of an index value determination method for determining an index value having a correlation with the mitochondrial activity of the subject,
A concentration value acquisition step of continuously or intermittently acquiring the concentration value of the acetone released from the subject who has ingested at least one selected from the acetone-generating species,
An index value determining step of determining the index value having a correlation with the mitochondrial activity of the subject using at least the acquired acetone concentration value.
Further, the characteristic configuration of the index value determination method according to the present invention for achieving the above object,
A subject who has ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate, and acetoacetic acid, which are acetone-producing species that are finally decomposed in the body to generate acetone. A concentration value obtaining step of continuously or intermittently obtaining the concentration value of the acetone released from the
An index value determining step of determining an index value having a correlation with the mitochondrial activity of the subject using at least the acquired acetone concentration value.

  In the characteristic configuration according to the index value determination system and the index value determination method according to the present invention, first, the concentration value of acetone released from a subject who has ingested at least one selected from acetone-generating species is continuously measured. Acquired periodically or intermittently. That is, in the present invention, in order to artificially create a state in which carbohydrate restriction or the like has been performed (a state in which fat is decomposed and ketone bodies such as 3-hydroxybutyric acid are supplied) in the body of the subject, At least one selected from among acetone-producing species, 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate, and acetoacetic acid is ingested by the subject and released from the subject. It obtains the concentration value of acetone.

  In this way, for example, when subjects having different health conditions and sports abilities take at least one of the same amount of acetone-producing species, the subjects obtain the same amount according to the mitochondrial activity of each subject. Changes in the concentration of acetone, and when the same subject ingests at least one of the different amounts of acetone-generating species, the concentration of acetone obtained varies according to the amount of intake. Will do.

  Then, an index value having a correlation with the mitochondrial activity of the subject is determined using at least the acquired acetone concentration value.

  As described above, an index value having a correlation with mitochondrial activity can be determined, and the mitochondrial activity of the subject can be easily grasped from this index value without using cells or the like. Then, for this index value, for example, a map in which the relationship between the index value and the intake of the acetone-generating species and the sex, age, lifestyle, exercise, presence / absence of illness, etc. of the subject is created in advance. By doing so, detection of lifestyle-related disease prevention groups, measurement of aging index, estimation of calories available per day, screening of foods that affect mitochondrial activity and verification of dietary habits, various diseases and mitochondrial activity Verification of relationship, verification of relationship between longevity and mitochondrial activity, verification of exercise training effect and setting of optimal training amount, confirmation of mental stress based on short-term reduction of mitochondrial activity, measurement of glycolysis and TCA cycle balance, mitochondria It can also be used for grasping disease states.

  As described above, according to the index value determination system and the index value determination method of the present invention, the concentration value of acetone released from the subject is acquired, and the mitochondrial activity is determined based on the acquired concentration value of acetone. Since it is possible to determine an index value having a correlation with, it is possible to easily grasp mitochondrial activity from the determined index value without complicated measurement work, as compared with a conventional measurement method requiring cells and the like. be able to.

Further, a further characteristic configuration of the index value determination system according to the present invention, in the concentration value obtaining means, to obtain a reference concentration value of acetone released from a subject who has not ingested the acetone generating species,
The index value determining means determines an acetone concentration increasing rate in a predetermined section until the acetone concentration value reaches the maximum concentration value from the reference concentration value as the index value.
Further characteristic configuration of the index value determination method according to the present invention, in the concentration value obtaining step, to obtain a reference concentration value of acetone released from a subject who has not ingested the acetone generating species,
In the index value determining step, an acetone concentration increasing rate in a predetermined section until the acetone concentration value reaches the maximum concentration value from the reference concentration value is determined as the index value.

  In each of the above-described features, the acetone concentration increasing rate is determined as an index value. When a subject ingests a certain amount of acetone-generating species, the concentration of acetone released from the subject increases with an increase in the blood concentration of the acetone-generating species, but the higher the mitochondrial activity, Since the amount of acetoacetic acid to be treated increases, the generation of acetone due to the decomposition of acetoacetic acid can be suppressed. That is, the higher the mitochondrial activity, the lower the acetone concentration increasing rate. Therefore, mitochondrial activity can be determined by using the acetone concentration increasing rate as an index value.

Further, a further characteristic configuration of the index value determination system according to the present invention is that the index value determination means maintains the concentration value within a predetermined range for a predetermined time after the acetone concentration value reaches a maximum concentration value. Thus, the minimum intake of the acetone-producing species is determined as the index value.
A further characteristic configuration of the index value determining method according to the present invention is such that, in the index value determining step, after the acetone concentration value reaches a maximum concentration value, a concentration value within a predetermined range is maintained for a predetermined time. That is, the minimum intake amount of the acetone-producing species is determined as the index value.

  In each of the above-described features, after the acetone concentration value reaches the maximum concentration value, the minimum intake amount of the acetone-generating species that maintains a concentration value within a predetermined range for a certain period of time is determined as the index value. I have to. According to the findings of the present inventors, if the intake of the acetone-generating species ingested by the subject does not exceed the amount that the mitochondria can handle, the acetone concentration value decreases after reaching the maximum value. On the other hand, when the amount of mitochondria exceeds the amount that can be processed, the concentration value of acetone reaches the maximum value and then maintains the concentration value within a predetermined range for a certain period of time. Therefore, the higher the mitochondrial activity, the greater the minimum intake of the acetone-generating species, which will maintain the concentration within a predetermined range for a period of time after the acetone concentration reaches the maximum concentration. Therefore, the mitochondrial activity can be grasped by using the minimum intake of the acetone-generating species as an index value as described above.

Further, a further characteristic configuration of the index value determination system according to the present invention is that the subject who has ingested at least one selected from the acetone-producing species, together with the acetone-producing species, ingest nutrients. There is in the point.
A further characteristic configuration of the index value determination method according to the present invention is that the subject who has ingested at least one selected from the acetone-producing species is ingesting nutrients together with the acetone-producing species. It is in.

  According to the findings newly found by the present inventors, when the subject is ingesting nutrients together with the acetone-generating species, the acetone concentration value to be obtained is lower than when the subject is ingesting only the acetone-generating species. And the measurement can be performed with good reproducibility. This is presumed to be due to the following reasons.

  That is, when the subject is hungry at the time of measurement, or when the subject is in a state where insulin is excessively secreted due to eating a diet high in sugar, the subject falls into a hypoglycemic state. May be. When the subject is in a hypoglycemic state, the ingested acetone-producing species is used for generating energy, and the amount of acetone-producing species used for generating energy fluctuates during the measurement. Since the amount of the generated acetone fluctuates accordingly, there is a possibility that the acquired acetone concentration value fluctuates in accordance with the amount of generated energy. However, when nutrients are taken along with the acetone-producing species, the intake of nutrients increases the blood sugar level and suppresses the production of energy using the acetone-producing species. It is presumed that this is because the acetone concentration value can be obtained in a state where the amount does not easily change during the measurement.

  According to each of the above-described features, since the subject takes nutrients together with the acetone-producing species, the subject may be hungry at the time of measurement or may have low blood sugar due to excessive secretion of insulin. Even in the state, it is possible to suppress the generation of energy using the ingested acetone-producing species, and the acetone concentration in a state where the fluctuation of the amount of acetone-producing species during measurement due to the generation of energy is suppressed Since the value can be obtained, the reliability of the obtained acetone concentration value is increased, and the measurement can be performed with good reproducibility.

Further, the characteristic configuration of the mitochondrial activity evaluation system according to the present invention,
Any one of the index value determination systems,
Based on the determined index value, comprising an activity evaluation means for evaluating mitochondrial activity of the subject,
In the activity evaluation means, the determined index value is compared with a past index value for the same subject, and the mitochondrial activity of the subject is evaluated.
Further, using the mitochondrial activity evaluation system, the characteristic configuration of the mitochondrial activity evaluation method for evaluating the mitochondrial activity of the subject,
A concentration value acquisition step of continuously or intermittently acquiring the concentration value of the acetone released from the subject who has ingested at least one selected from the acetone-generating species,
An index value determining step of determining the index value having a correlation with the mitochondrial activity of the subject using at least the concentration value of the obtained acetone,
Based on the determined index value, performing an activity evaluation step of evaluating the mitochondrial activity of the subject,
In the activity evaluation step, the determined index value is compared with a past index value for the same subject to evaluate mitochondrial activity of the subject.
Further, the characteristic configuration of the mitochondrial activity evaluation method according to the present invention,
After the index value is determined by any one of the index value determination methods,
Based on the determined index value, performing an activity evaluation step of evaluating the mitochondrial activity of the subject,
In the activity evaluation step, the determined index value is compared with a past index value for the same subject to evaluate mitochondrial activity of the subject.

  In the characteristic configuration according to the mitochondrial activity evaluation system and the mitochondrial activity evaluation method according to the present invention, first, a concentration value of acetone released from a subject who has ingested at least one selected from acetone-producing species is continuously measured. Acquired periodically or intermittently. Then, an index value having a correlation with the mitochondrial activity of the subject is determined using at least the acquired acetone concentration value. Thereafter, the index value is compared with a past index value for the same subject to evaluate the mitochondrial activity of the subject. Thus, by comparing the obtained index value with the past index value for the same subject, the change in mitochondrial activity of the subject, that is, the current mitochondrial activity is higher than the past mitochondrial activity. It can be evaluated whether it is low or low. By being able to evaluate mitochondria, detection of lifestyle-related disease prevention groups, measurement of aging index, estimation of calories available per day, screening of foods that affect mitochondrial activity, and verification of dietary habits , Verifying the relationship between various diseases and mitochondrial activity, verifying the relationship between longevity and mitochondrial activity, verifying the effects of exercise training and setting the optimal training amount, confirming mental stress based on short-term decline in mitochondrial activity, This makes it possible to measure the balance of the TCA cycle, grasp the state of mitochondrial disease, and the like.

It is a block diagram showing a schematic structure of an index value determination device and a mitochondrial activity evaluation device according to the present embodiment. It is a flowchart which shows the index value determination method and mitochondrial activity evaluation method which concern on this embodiment. It is a graph which shows the relationship between the elapsed time after ingesting the acetone-generating species, the increase in the blood 3HB concentration, and the increase in the acetone concentration. It is a graph which shows the relationship between the elapsed time after ingesting the acetone-generating species, the increase in the blood 3HB concentration, and the increase in the acetone concentration. It is a graph which shows the relationship between the elapsed time after ingesting the acetone-generating species, the increase in the blood 3HB concentration, and the increase in the acetone concentration. It is a graph which shows the relationship between the elapsed time after ingesting the acetone-generating species, the increase in the blood 3HB concentration, and the increase in the acetone concentration. It is a graph which shows the relationship between the elapsed time after ingesting the acetone generation | occurrence | production species, and the amount of change of acetone concentration. It is a graph which shows the relationship between the elapsed time after ingesting the acetone generation | occurrence | production species and sugar, and the amount of change of acetone concentration.

[First Embodiment]
Hereinafter, an index value determination device and a mitochondrial activity evaluation device according to the first embodiment will be described with reference to the drawings.

  As shown in FIG. 1, the mitochondrial activity evaluation device 1 according to the present embodiment includes a concentration value acquiring unit 2 (concentration value acquiring unit) for acquiring a concentration value of acetone, and a concentration value acquired by the concentration value acquiring unit 2. And an index value output unit 3 (index value determining means) for determining and outputting an index value having a correlation with the mitochondrial activity of the subject, and an index value output from the index value output unit 3. An activity evaluation unit 5 (activity evaluation means) for evaluating mitochondrial activity of the examiner and an index value storage unit 6 for storing index values are provided. The determination device 4.

  The concentration value acquisition unit 2 acquires the concentration value of acetone from the breath sensor 10 that detects acetone contained in the breath of the subject, and transmits the acquired concentration value to the index value output unit 3. The detection result from the breath sensor 10 is transmitted to the concentration value acquisition unit 2 by wireless communication or wired communication.

  The index value output unit 3 determines an acetone concentration increasing speed as an index value based on the concentration value received from the index value output unit 3 and transmits the determined value to the activity evaluation unit 5 or the display device 11 provided as appropriate. Specifically, in the present embodiment, it is selected from among acetone-producing species, 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate, and acetoacetic acid, which are finally decomposed in the body to generate acetone. Concentration of acetone in the breath of a subject who has taken at least one of the above, and the concentration of acetone contained in the breath of a subject who has not taken an acetone-generating species (reference concentration value) Based on the above, the acetone concentration increasing speed in a predetermined section until the acetone concentration value reaches the maximum concentration value from the reference concentration value is determined as an index value. When the rate of increase in acetone concentration is used as an index value, the higher the mitochondrial activity, the lower the rate of increase in acetone concentration. The display device 11 may be incorporated in the mitochondrial activity evaluation device 1 or the index value determination device 4, or may be separately provided outside these devices.

  The activity evaluation unit 5 determines whether or not the acetone concentration increasing speed received from the index value output unit 3 is equal to or higher than a predetermined speed. If the speed is not equal to or higher than the predetermined speed, a signal for displaying that fact is displayed on the display device 11. Send to On the other hand, when the acetone concentration increasing speed is equal to or higher than the predetermined speed, the received acetone concentration increasing speed is transmitted to and stored in the index value storage unit 6, and the past acetone concentration of the same subject is stored in the index value storage unit 6. Check whether the concentration increase rate is memorized, and if so, compare the received acetone concentration increase rate with the past acetone concentration increase rate for the same subject, and the mitochondrial activity is It evaluates whether it is decreasing or increasing, and transmits the result to the display device 11.

  Next, an index value determination method and a mitochondrial activity evaluation method will be described with reference to FIG. First, in step # 1, a reference density value is measured. Specifically, the breath sensor 10 detects acetone contained in the breath of the subject who has not ingested the acetone-generating species, and acquires the acetone concentration value (reference concentration value). When the mitochondrial activity evaluation device 1 is used, the detection result of the breath sensor 10 is transmitted to the concentration value acquiring unit 2 to acquire a reference concentration value of acetone. Sent to.

  Next, in step # 2, the subject ingests the acetone-producing species. In addition, the amount of the acetone-generating species to be ingested by the subject is an appropriate amount determined for each subject in accordance with the health condition, sports ability, and the like. If it is determined that the same subject is used, the same subject is ingested with the same amount of acetone-producing species in the index value determination method and mitochondrial activity evaluation method to be performed in the future. In addition, the intake amount of the acetone-generating species is preferably 0.5 g to 50 g, more preferably 1 g to 25 g, and most preferably 3 g to 10 g.

  Thereafter, in step # 3, the acetone concentration value is measured at regular intervals (concentration value acquisition step). That is, the acetone contained in the breath of the subject who has ingested the acetone-generating species is detected at regular intervals using the breath sensor 10, and the concentration value of acetone is acquired. When the mitochondrial activity evaluation device 1 is used, the detection result of the breath sensor 10 is transmitted to the concentration value acquisition unit 2 to acquire the concentration value of acetone, and this concentration value is transmitted to the index value output unit 3. Is done.

  Next, in step # 4, it is determined whether or not the maximum concentration value of acetone has been acquired. If the maximum concentration value has been acquired, the process proceeds to step # 5, and if the maximum concentration value has not been acquired. Returns to step # 3. Specifically, when the acquired density value is higher than the density value measured and obtained at the timing immediately before the timing at which this density value was measured, it is determined that the maximum density value has not been obtained, and Is determined to have acquired the maximum density value. When the mitochondrial activity evaluation device 1 is used, the index value output unit 3 determines whether or not the maximum concentration value of acetone has been acquired.

  As a process # 5, an acetone concentration increasing speed as an index value is determined (index value determining step). Specifically, based on the concentration value and the elapsed time at a predetermined timing until the acetone concentration value reaches the maximum concentration value from the reference concentration value, and based on the reference concentration value, the acetone concentration value is used as a reference. The rate of increase in acetone concentration from the concentration value to the concentration value at a predetermined timing is determined as an index value. When the mitochondrial activity evaluation device 1 is used, the index value output unit 3 calculates an acetone concentration increasing speed, determines the acetone concentration increasing speed as an index value, and determines the determined acetone concentration increasing speed as an activity evaluating unit. 5 or to the display device 11. The predetermined timing is, for example, a timing at which the rate of increase in the concentration of acetone becomes constant. In the case where the mitochondrial activity evaluation device 1 is used, an index based on the measured data indicates that the rate of increase in the concentration of acetone becomes constant. This is the timing determined by the value output unit 3. Note that the acetone concentration increasing rate as the index value may be calculated based on the reference concentration value and the maximum concentration value, and the time required to reach the maximum concentration value from the reference concentration value.

  Steps # 1 to # 5 correspond to an index value determination method. By performing steps # 1 to # 5 as described above, the acetone concentration as an index value having a correlation with mitochondrial activity is determined. Since the rate of increase can be determined, the mitochondrial activity of the subject can be easily grasped from this index value without using cells or the like. The index value thus determined, for example, pre-defined the relationship between the index value and the intake of the acetone-generating species and the sex of the subject, age, lifestyle, the presence or absence of exercise, the presence or absence of disease, etc. By creating a map, detection of lifestyle-related disease prevention group, measurement of aging index, estimation of calories available per day, screening of foods that affect mitochondrial activity and verification of dietary habits, various diseases Of mitochondrial activity, longevity and mitochondrial activity, effect of exercise training and setting of optimal training amount, confirmation of mental stress based on short-term decrease of mitochondrial activity, confirmation of glycolysis and TCA cycle It can also be used for balance measurement, grasping the state of mitochondrial disease, and the like.

  In step # 6, it is determined whether or not the determined acetone concentration increasing speed is equal to or higher than a predetermined speed. If it is determined that the speed is higher than the predetermined speed, the process proceeds to step # 7. On the other hand, when it is determined that the speed is lower than the predetermined speed, the process returns to the step # 2 to increase the intake amount of the acetone-generating species, and then the process returns to the step # 3. This indicates that the rate of increase in the acetone concentration was not sufficiently correlated with the mitochondrial activity of the subject because the amount of acetone-generating species ingested by the subject was sufficient to process mitochondria. Is high.

  In step # 7, it is determined whether or not a past acetone concentration increase rate for the same subject exists. If so, the process proceeds to step # 8, and if not, the process ends. Then, in step # 8, comparing the acetone concentration increasing rate determined this time with the past acetone concentration increasing rate for the same subject, whether the mitochondrial activity of the subject is higher than in the past? Or, it is evaluated whether it is low (activity evaluation step).

  When the mitochondrial activity evaluation apparatus 1 is used for these steps # 6 to # 8, the activity evaluation unit 5 stores the determined acetone concentration increasing speed in the index value storage unit 6 and the acetone concentration increasing speed. Is determined whether or not is equal to or higher than a predetermined speed (step # 6). If it is determined that the speed is equal to or higher than the predetermined speed, the past acetone concentration for the same subject is referred to by referring to the index value storage unit 6. It is determined whether or not the increase speed is stored (step # 7). If the increase speed is stored, the acetone concentration increase speed is compared with the past acetone concentration increase speed for the same subject, and the test is performed. It is evaluated whether the mitochondrial activity of the person is higher or lower than in the past, and the result is transmitted to the display device 11. On the other hand, when it is determined that the past acetone concentration increase rate for the same subject is not stored, the process ends.

  In this way, by using the acetone concentration increase rate as an index value of mitochondrial activity, it is possible to evaluate whether the mitochondrial activity of the same subject is higher or lower than the past results. It is possible, for example, to determine the rate of increase in acetone concentration as an index value for each subject in a regular health check or the like, how the mitochondrial activity has changed compared to the rate of increase in acetone concentration in the past. The subject can know.

  As described above, according to the index value determination method according to the present embodiment, it is possible to determine the acetone concentration increasing rate, which is an index value having a correlation with the mitochondrial activity of the subject, using this acetone concentration increasing rate Various tests and verifications on mitochondrial activity can be performed. In addition, by comparing the acetone concentration increase rate, which is an index value, with the past acetone concentration increase rate of the same subject, it is possible to inform the subject of how the mitochondrial activity has changed, and to observe lifestyle-related diseases. Can be given an opportunity to work on prevention of aging and aging.

  Hereinafter, specific Experimental Examples 1 to 4 will be described.

(Experimental example 1)
In the case of ingesting 1 g of 3-hydroxybutyrate (3HB salt) (10 ml of 10% 3HB neutralized with Na: Ca: Mg = 70: 15: 15), 0 minutes (before ingestion), 30 minutes, FIG. 3 shows the relationship between the increase in blood 3HB concentration (increase relative to 0 minutes) and the increase in acetone concentration in breath (increase relative to 0 minutes) after 60 minutes, 90 minutes, and 120 minutes. As for the acetone concentration value in the breath, 1 L of the breath was collected in a collection bag every time and analyzed by gas chromatography. Since the amount of 3HB salt ingested was small relative to the mitochondrial activity of subject A (52-year-old male), the amount of increase in blood 3HB concentration increased to 0.2 mM after 30 minutes, decreased to 0, and decreased during exhalation. The amount of increase in the acetone concentration also became a maximum at a low value of 0.1 ppm after 60 minutes, and then decreased immediately. If the change pattern of the increase amount of the acetone concentration value becomes a pattern that decreases immediately after the increase amount becomes the maximum, it is determined that it is necessary to increase the intake of 3HB salt and perform re-measurement. .
The rate of increase in the acetone concentration per hour from 0 minute to 60 minutes (0.096 ppm / hr) is lower than the rate of increase in the acetone concentration in Experimental Examples 2 to 4 to be described later. If is lower than a predetermined rate (for example, 0.1 ppm / hr), it may be determined that it is necessary to increase the amount of 3HB salt to be taken and perform remeasurement.
In addition, the peak of the increase in the acetone concentration in expiration appears later than the peak in the increase in the 3HB concentration in blood, because the acetone generated in mitochondria transfers to the body fluid and is released from the exhalation. This is probably because it takes time.
Further, based on the body water content (64 kg × 70% = 45 L) estimated from the body weight (64 kg) of the subject A and the intake amount of 3HB salt (1 g), the total amount of the ingested 3HB salt was transferred to the body fluid. The blood 3HB concentration was 1 g / 104 (3HB molecular weight) /45L=0.21 mM, which is almost the same as the measured value of 0.2 mM. Therefore, almost all of the ingested 3HB salt was transferred to the body fluid, and this measurement was performed. It is presumed that it was used for.

(Experimental example 2)
When 3 g of 3HB salt was ingested (30 ml of 10% 3HB neutralized with Na: Ca: Mg = 70: 15: 15), 0 minute (before ingestion), 30 minutes, 60 minutes, 90 minutes, 120 minutes FIG. 4 shows the relationship between the increase in the blood 3HB concentration (the increase with respect to 0 minutes) and the increase in the acetone concentration value in the breath (the increase with respect to 0 minutes) after one minute. As for the acetone concentration value in the breath, 1 L of the breath was collected in a collection bag at each time and analyzed by gas chromatography. Since the amount of 3HB salt ingested was sufficiently large relative to the mitochondrial activity of subject A (52-year-old male), the increase in blood 3HB concentration increased to 0.4 mM after 60 minutes and was then used in mitochondria. Decreased gradually. The increase amount of the acetone concentration in the breath increased to 0.9 ppm after 60 minutes, and then gradually decreased while maintaining the predetermined range. If the change pattern of the increase amount of the acetone concentration value becomes a pattern that maintains within a predetermined range after the increase amount becomes the maximum, it is determined that the measurement has been normally performed and it is not necessary to perform the re-measurement. Shall be.
In this case, the index value having a correlation with the activity of mitochondria may be an intake amount (3 g in the present experimental example) which keeps within a predetermined range after the increase in the concentration value of acetone reaches the maximum. Alternatively, the rate of increase in acetone concentration per hour from 0 minute to 60 minutes (0.798 ppm / hr) may be used. The latter is a simpler and more detailed index.

(Experimental example 3)
When 5 g of 3HB salt was ingested (50 ml of 10% 3HB neutralized with Na: Ca: Mg = 70: 15: 15), 0 minute (before ingestion), 30 minutes, 60 minutes, 90 minutes, 120 minutes FIG. 5 shows the relationship between the increase in blood 3HB concentration (increase relative to 0 minutes) and the increase in breath acetone concentration (increase relative to 0 minutes) after one minute. As for the acetone concentration value in the breath, 1 L of the breath was collected in a collection bag every time and analyzed by gas chromatography. Since the amount of 3HB salt ingested was sufficiently large relative to the mitochondrial activity of subject A (52-year-old male), the increase in blood 3HB concentration increased to 0.7 mM after 60 minutes, and was then used in mitochondria. Decreased gradually. Although the intake of 3HB salt is 5 times that of 1 g of Experimental Example 1, the maximum increase in the concentration of 3HB is 3.5 times because not all of the ingested 3HB can be consumed. It is thought that it is. The increase in the acetone concentration in the exhaled air gradually increased after increasing to 1.1 ppm after 90 minutes. Since the change pattern of the increase amount of the concentration value of acetone is a pattern that maintains within a predetermined range after the increase amount becomes maximum, the measurement can be performed normally as in the case of the experimental example 2 described above. It is determined that there is no need to perform re-measurement.
The rate of increase in acetone concentration per hour (0.756 ppm / hr) from 0 minute to 60 minutes as an index value was almost the same as that in Experimental Example 2. From this, the amount of 3HB salt ingested by the subject is more than the amount of intake such that the pattern of the increase in the concentration value of acetone becomes a pattern that maintains within a predetermined range after the increase becomes maximum. At most, there is no particular problem. Further, by continuously performing measurement using a sensor element or the like capable of detecting acetone, it is possible to more accurately calculate the acetone concentration increasing rate as an index value.

(Experimental example 4)
In the case of ingesting 3 g of 3HB salt (30 ml of 10% 3HB neutralized with Na: Ca: Mg = 70: 15: 15), 0 minute (before ingestion), 30 minutes, 60 minutes, and 90 minutes after ingestion FIG. 6 shows the relationship between the increase in blood 3HB concentration (increase relative to 0 minutes) and the increase in breath acetone concentration (increase relative to 0 minutes). As for the acetone concentration in the breath, 1 L of the breath was collected in a collection bag every time and analyzed by gas chromatography. Since the amount of 3HB ingested was sufficiently large relative to the mitochondrial activity of subject B (59-year-old male), the increase in blood 3HB concentration increased to 0.7 mM after 60 minutes, and was then gradually used by mitochondria. did. The increase in the acetone concentration in the breath increased to 0.8 ppm after 30 minutes, and then decreased gradually. If the pattern of the increase in the concentration of acetone becomes like this, the measurement is determined to be successful. The rate of increase in the acetone concentration per hour (1.602 ppm / hr) from 0 minutes to 30 minutes as the activity of mitochondria was almost twice as large as that of the subject A in Experimental Examples 2 and 3. It is considered that since the subject B was older and had lower mitochondrial activity, the utilization rate of acetoacetic acid by mitochondria was slower, and the acetone concentration rate was faster because more acetone was generated.

[Second embodiment]
In the second embodiment, a test subject ingesting at least one selected from among acetone-producing species, 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate, and acetoacetic acid, produces acetone-producing species. The difference from the first embodiment is that the nutrients are ingested simultaneously with the seeds.

  That is, in the second embodiment, the mitochondrial activity evaluation device 1 measures the concentration value of acetone contained in the breath of the subject who has ingested nutrients simultaneously with the acetone-producing species, and the state in which the acetone-producing species and nutrients are not ingested. Based on the concentration (reference concentration value) of acetone contained in the breath of the subject, the acetone concentration increasing speed is determined as an index value, and the subject is determined based on the determined index value, the acetone concentration increasing speed. To assess mitochondrial activity. The “nutrient” in the present application is not particularly limited as long as it is converted into glucose in the body, and examples thereof include sugars, carbohydrates, proteins, amino acids, lipids, and dietary fiber. The subject may take only one of them, or a combination of a plurality of them, together with the acetone-producing species.

  As described above, since the subject is taking nutrients at the same time as the acetone-producing species, the subject may be hungry at the time of measurement or may have low blood sugar due to excessive secretion of insulin. Even in the state, it is possible to suppress the generation of energy using the ingested acetone-producing species, and the acetone concentration in a state where the fluctuation of the amount of acetone-producing species during measurement due to the generation of energy is suppressed Since the value can be obtained, the reliability of the obtained acetone concentration value is increased, the measurement can be performed with good reproducibility, and the evaluation accuracy of mitochondrial activity can be improved.

  Hereinafter, an experiment performed to confirm the effect of ingesting nutrients simultaneously with the acetone-producing species will be described.

  5 g of 3HB was dissolved in 100 ml of water and the sample was adjusted to pH 4 with potassium hydroxide (sample 1), and 5 g of 3HB and 2 g of sugar were dissolved in 100 ml of water and adjusted to pH 4 with potassium hydroxide (sample 2) is prepared, and the subject C is ingested by taking these samples 1 and 2. The breath of the subject C in a resting state before the sample is taken and every time a predetermined time elapses after the sample is taken. Was collected and analyzed by gas chromatography to measure the acetone concentration in the breath. FIG. 7 is a graph showing the relationship between the elapsed time after ingestion of the sample and the amount of change in the acetone concentration value (the amount of change from before ingestion) in the case of ingesting sample 1, and FIG. It is a graph which shows the relationship between the elapsed time after ingestion of a sample, and the amount of change of the acetone concentration value (the amount of change before ingestion) about the case. In addition, two experiments in which sample 1 was taken in the morning (“AM 1” and “AM 2” in FIG. 7), and two experiments in which sample 1 was taken in the afternoon (“PM 1” in FIG. 7, "Afternoon 2"), two experiments in which sample 2 was taken in the morning ("am + nutrition 1" and "am + nutrition 2" in Fig. 8), and two experiments in which sample 2 was taken in the afternoon (Fig. A total of eight experiments (“afternoon + nutrition 1” and “afternoon + nutrition 2” in 8) were performed on different days.

  Comparing the graphs for each experiment when sample 1 was ingested, it can be seen that the variation was large as shown in FIG. Specifically, the minimum value and the maximum value of the change amount of the acetone concentration value after a lapse of a predetermined time from the ingestion of the sample 1 are -119 ppb (2 pm) and 31 ppb (maximum) after 15 minutes. 1), the minimum value is -37 ppb (2 am) and the maximum value is 26 ppb (1 am) after 30 minutes, and the minimum value is -35 ppb (1 pm) after 45 minutes. The maximum value was 223 ppb (2 am), and after 60 minutes, the minimum value was 93 ppb (1 am) and the maximum value was 287 ppb (2 am).

  On the other hand, when comparing the graphs of the respective experiments in the case of ingesting the sample 2, it can be seen that the variation is smaller than in the case of ingesting the sample 1, as shown in FIG. Specifically, the minimum value and the maximum value of the change amount of the acetone concentration value after a predetermined time has elapsed from the ingestion of the sample 2 are 19 ppb (am + nutrition 1) and the maximum value are 75 ppb after 15 minutes. (Pm + nutrition 2), the minimum value is 86 ppb (am + nutrition 1), the maximum value is 196 ppb (pm + nutrition 2) after 30 minutes, and the minimum value is 45 minutes after 45 minutes. 234 ppb (am + nutrition 1), the maximum value is 302 ppb (am + nutrition 2), and after 60 minutes, the minimum value is 355 ppb (pm + nutrition 2) and the maximum value is 539 ppb (am + nutrition 2). there were.

  As described above, the variation in the degree of variation between the case where sugar was ingested at the same time as 3HB and the case where sugar was not taken was due to the fact that sugar was not taken at the same time as 3HB, Is in a state of low blood sugar due to being hungry or a state of excessive secretion of insulin due to eating a diet high in carbohydrates, and the ingested 3HB is used for generation of energy, When the amount of 3HB used for generation fluctuates during the measurement, the amount of generated acetone fluctuates accordingly, and as a result, the obtained acetone concentration value fluctuates according to the amount of generated energy. However, when the sugar is ingested simultaneously with 3HB, the blood sugar level increases due to the sugar ingestion, and the generation of energy using 3HB is suppressed. Because, with the amount of 3HB used for generating the energy is hardly changed during the measurement, and can obtain the acetone concentration value, it is assumed that variation is small.

[Another embodiment]
[1] In the above-described embodiment, the aspect in which the acetone concentration increasing speed is used as the index value has been described, but the present invention is not limited to this. As an index value having a correlation with mitochondrial activity, an acetone-generating species that maintains a concentration value within a predetermined range for a certain period of time after the acetone concentration value reaches the maximum concentration value instead of the acetone concentration increasing rate. May be used. In addition, the above-mentioned fixed time is 5 to 30 minutes, preferably 5 to 10 minutes, and the above-mentioned predetermined range is ± 30% of the maximum density value, preferably ± 20% of the maximum density value. . If the amount of acetone-generating species ingested by the subject does not exceed the amount that mitochondria can handle, the concentration of acetone decreases after reaching the maximum value, while mitochondria can handle If the amount is exceeded, the concentration value of acetone will maintain a concentration value within a predetermined range for a certain period of time after reaching the maximum value. Therefore, the higher the mitochondrial activity, the greater the minimum intake of the acetone-generating species, which will maintain the concentration within a predetermined range for a period of time after the acetone concentration reaches the maximum concentration. Therefore, the mitochondrial activity can be grasped even when the minimum intake of the acetone-generating species as described above is used as an index value.

[2] In the above embodiment, the acetone contained in the breath of the subject is detected at regular intervals, that is, intermittently using the breath sensor. However, the present invention is not limited to this. You may make it detect acetone continuously and continuously. Further, the sensor for detecting acetone is not limited to the breath sensor, and a skin sensor capable of detecting acetone released from the skin of the subject can be used.

[3] In the above embodiment, the mode in which the index value is transmitted from the activity evaluation unit 5 to the index value storage unit 6 and stored is exemplified. However, the present invention is not limited to this, and the index value output unit outputs the index value storage. The index value may be transmitted to and stored in the unit, or an appropriate storage unit for storing the density value obtained by the density value obtaining unit may be provided.

[4] In the above embodiment, the index value output unit 3 determines and outputs the acetone concentration increasing rate as the index value, but does not necessarily output the index value, and stores the index value. In addition, the activity evaluation unit may appropriately access and acquire the information.

[5] The mitochondrial activity evaluation method and index value determination method can be performed without using a mitochondrial activity evaluation device and an index value determination device.

[6] In the above-described second embodiment, the aspect in which the subject is ingesting nutrients simultaneously with the acetone-producing species has been described. However, the present invention is not limited to this. Nutrition may be ingested after the infested species is ingested.

  An index value determining system and an index value determining method capable of determining an index value enabling easy grasp of mitochondrial activity, and a mitochondrial activity evaluation system capable of easily evaluating mitochondrial activity based on the index value and It can be used for a method for evaluating mitochondrial activity.

1 mitochondrial activity evaluation device (mitochondrial activity evaluation system)
2 Density value acquisition unit (density value acquisition means)
3 index value output unit (index value determination means)
4 Index value determination device (index value determination system)
5 Activity evaluation section (activity evaluation means)

Claims (12)

A subject who has ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate, and acetoacetic acid, which are acetone-producing species that are finally decomposed in the body to generate acetone. Concentration value acquisition means for continuously or intermittently acquiring the concentration value of the acetone released from the
An index value determining unit that determines an index value having a correlation with the mitochondrial activity of the subject using at least the acquired acetone concentration value. In the concentration value obtaining means, to obtain a reference concentration value of acetone released from a subject who has not ingested the acetone generating species,
2. The index value determination system according to claim 1, wherein the index value determination unit determines, as the index value, an acetone concentration increase rate in a predetermined section until the acetone concentration value reaches the maximum concentration value from the reference concentration value. 3.   In the index value determining means, after the concentration value of the acetone reaches the maximum concentration value, for a certain period of time, the concentration value within a predetermined range will be maintained, the minimum intake of the acetone generating species as the index value. 2. The index value determination system according to claim 1, wherein the index value is determined.   The index value determination according to any one of claims 1 to 3, wherein the subject who has taken at least one selected from the acetone-producing species is taking nutrients together with the acetone-producing species. system. An index value determination system according to any one of claims 1 to 4,
Based on the determined index value, comprising an activity evaluation means for evaluating mitochondrial activity of the subject,
A mitochondrial activity evaluation system for evaluating the mitochondrial activity of the subject by comparing the determined index value with a past index value for the same subject in the activity evaluation means. A method for determining an index value having a correlation with mitochondrial activity of the subject, using the index value determination system according to any one of claims 1 to 4,
A concentration value acquisition step of continuously or intermittently acquiring the concentration value of the acetone released from the subject who has ingested at least one selected from the acetone-generating species,
An index value determining step of determining the index value having a correlation with the mitochondrial activity of the subject using at least the acquired acetone concentration value. A method for evaluating mitochondrial activity of the subject, using the mitochondrial activity evaluation system according to claim 5,
A concentration value acquisition step of continuously or intermittently acquiring the concentration value of the acetone released from the subject who has ingested at least one selected from the acetone-generating species,
An index value determining step of determining the index value having a correlation with the mitochondrial activity of the subject using at least the concentration value of the obtained acetone,
Based on the determined index value, performing an activity evaluation step of evaluating the mitochondrial activity of the subject,
In the activity evaluation step, a mitochondrial activity evaluation method for evaluating the mitochondrial activity of the subject by comparing the determined index value with a past index value for the same subject. A subject who has ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate, and acetoacetic acid, which are acetone-producing species that are finally decomposed in the body to generate acetone. A concentration value obtaining step of continuously or intermittently obtaining the concentration value of the acetone released from the
An index value determining step of determining an index value having a correlation with the mitochondrial activity of the subject using at least the acquired acetone concentration value. In the concentration value obtaining step, to obtain a reference concentration value of acetone released from a subject who has not ingested the acetone generating species,
9. The index value determining method according to claim 8, wherein, in the index value determining step, an acetone concentration increasing rate in a predetermined section until the acetone concentration value reaches the maximum concentration value from the reference concentration value is determined as the index value.   In the index value determination step, after the concentration value of the acetone reaches the maximum concentration value, for a certain period of time, the concentration value within a predetermined range will be maintained, and the minimum intake of the acetone-producing species will be used as the index value. The index value determination method according to claim 8, wherein the index value is determined.   The index value determination according to any one of claims 8 to 10, wherein the subject who has ingested at least one selected from the acetone-producing species is taking nutrients together with the acetone-producing species. Method. After determining the index value by the index value determination method according to any one of claims 8 to 11,
Based on the determined index value, performing an activity evaluation step of evaluating the mitochondrial activity of the subject,
In the activity evaluation step, a mitochondrial activity evaluation method for evaluating the mitochondrial activity of the subject by comparing the determined index value with a past index value for the same subject.

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