JP7361517B2 - Index value determination system, mitochondrial activity evaluation system, index value determination method, and mitochondrial activity evaluation method - Google Patents

Description

The present invention provides an index value determination system and an index value determination method for determining an index value that correlates with the mitochondrial activity of a subject, and a mitochondrial activity evaluation system and mitochondrial activity evaluation method for evaluating mitochondrial activity based on the index value. Regarding.

Mitochondria are important organs that produce energy within cells, and have the function of converting ingested nutrients into ATP (adenosine triphosphate), an energy storage substance, but active oxygen is generated during the conversion, so Mitochondrial activity gradually decreases due to aging and other factors. Recent research has revealed that when mitochondrial activity decreases, even more active oxygen is generated, which causes aging and various diseases. Therefore, understanding mitochondrial activity will contribute 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 mitochondrial metabolic activity uses cells collected from living organisms such as mammals or cultured cells, and permeabilizes the cells with a solution containing streptolysin O. This is a method to measure the energy metabolic activity of. According to this method for measuring mitochondrial metabolic activity, metabolic activity can be measured without damaging the mitochondrial membrane.

Japanese Patent Application Publication No. 2011-205935

From the perspective that understanding mitochondrial activity contributes to prevention of aging and lifestyle-related diseases, for example, it can be measured as one of the test items in a health checkup, or it can be measured by the examinee himself on a daily basis. It is important that mitochondrial activity can be easily measured and understood without any complicated work.

However, the method for measuring mitochondrial metabolic activity described in Patent Document 1 requires the use of cells removed from the body, making the measurement work complicated and making it impossible to easily measure mitochondrial activity. Therefore, mitochondrial activity cannot be easily determined.

The present invention was made in view of the above circumstances, and provides an index value determination system and an index value determination method that can determine an index value that enables easy understanding of mitochondrial activity, as well as The purpose is to provide a mitochondrial activity evaluation system and a mitochondrial activity evaluation method that can easily evaluate the activity.

Therefore, in order to achieve the above objective, the inventor of the present application has conducted extensive research on methods that can easily grasp mitochondrial activity, and as a result has found a correlation between the concentration value of acetone released outside the body and mitochondrial activity. We found that mitochondrial activity can be understood by focusing on the acetone concentration and determining an index value that correlates with mitochondrial activity based on the acetone concentration value, and further discovered that mitochondrial activity can be evaluated using this index value. Ta.

In other words, when carbohydrates are restricted, etc., there is a shortage of sugar in the body, so the body breaks down fat in the body to generate ketone bodies, and uses these ketone bodies to create energy in the mitochondria. Specifically, fatty acids produced by fat decomposition are broken down into 3-hydroxybutyric acid within the mitochondria, which is then oxidized to acetoacetic acid. Acetoacetic acid is then taken into the TCA cycle (citric acid cycle) via acetoacetyl-CoA and used as energy.

At this time, if there is not enough mitochondrial activity to consume the acetoacetic acid supplied by fat decomposition, the consumption of the supplied acetoacetic acid cannot keep up, and the acetoacetic acid is decomposed into acetone and carbon dioxide, leaving the mitochondria. The acetone odor is emitted from the body when acetone is released into body fluids with exhalation or evaporates from the skin.

In other words, when mitochondrial activity is high, the amount of acetoacetate consumed in the body increases, thereby decreasing the concentration value of acetone released outside the body, and conversely, when mitochondrial activity is low, the amount of acetoacetate consumed decreases. Therefore, the concentration value of acetone released outside the body increases. In this way, there is a correlation between the concentration of acetone released outside the body and mitochondrial activity, so by intentionally increasing the amount of ketone bodies in the body, we can reduce the amount of acetone generated by the subject. Once detected, mitochondrial activity can be determined by determining an index value that correlates with mitochondrial activity based on the acetone concentration value, and furthermore, 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 as follows:
A subject who ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate ester, and acetoacetic acid, which are acetone-generating species that are ultimately decomposed in the body to generate acetone. Concentration value acquisition means that continuously or intermittently acquires the concentration value of the acetone released from the
The method further comprises 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, the characteristic configuration of an index value determination method for determining an index value having a correlation with the mitochondrial activity of the subject using the index value determination system is as follows:
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-producing species;
The present invention is characterized in that an index value determining step is performed, using at least the acquired acetone concentration value, to determine the index value that has a correlation with the mitochondrial activity of the subject.
Further, the characteristic structure of the index value determination method according to the present invention for achieving the above object is as follows:
A subject who ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate ester, and acetoacetic acid, which are acetone-generating species that are ultimately decomposed in the body to generate acetone. a concentration value acquisition step of continuously or intermittently acquiring the concentration value of the acetone released from the
The present invention is characterized in that an index value determination step is executed, in which an index value having a correlation with the mitochondrial activity of the subject is determined using at least the acquired acetone concentration value.

In the characteristic configuration of the index value determination system and 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 the acetone-producing species is continuously determined. Acquired regularly or intermittently. That is, in the present invention, in order to simulate a state in which carbohydrates are restricted (a state in which fat is decomposed and ketone bodies such as 3-hydroxybutyric acid are supplied) in the subject's body, A test subject ingests at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate ester, and acetoacetic acid, which are acetone-generating species, and is released from the test subject. I am trying to obtain the concentration value of acetone.

By doing this, for example, when subjects with different health conditions, sports abilities, etc. ingest the same amount of at least one of the acetone-producing species, it is possible to obtain information according to the mitochondrial activity of each subject. When the same subject ingests different amounts of at least one of the acetone-producing species, the acetone concentration value obtained changes depending on the intake amount. I will do it.

Then, using at least the obtained acetone concentration value, an index value that correlates with the mitochondrial activity of the subject is determined.

In this way, an index value that has a correlation with mitochondrial activity can be determined, and the mitochondrial activity of the subject can be easily understood from this index value without using cells or the like. This index value can be determined by creating a map in advance that specifies the relationship between the index value and the amount of acetone-producing species ingested, the gender, age, lifestyle habits, presence or absence of exercise, presence or absence of disease, etc. of the subject. By using this product, you can detect lifestyle-related disease prevention groups, measure aging indicators, estimate daily calorie intake, screen for foods that affect mitochondrial activity, verify dietary habits, and correlate various diseases with mitochondrial activity. Verification of the relationship, verification of the relationship between longevity and mitochondrial activity, verification of the effects of exercise training and setting of optimal training amount, confirmation of mental stress based on short-term decrease in mitochondrial activity, measurement of the balance between glycolysis and TCA cycle, mitochondrial It can also be used to understand the state of illness.

As described above, according to the index value determination system and index value determination method according to the present invention, the concentration value of acetone released from the subject is acquired, and based on the acquired concentration value of acetone, mitochondrial activity is determined. Because it is possible to determine index values that correlate with be able to.

Further, a further characteristic configuration of the index value determination system according to the present invention is that the concentration value acquisition means acquires a reference concentration value of acetone released from a subject who has not ingested the acetone-generating species;
In the index value determining means, the acetone concentration increasing rate in a predetermined interval from the reference concentration value to the maximum concentration value is determined as the index value.
A further characteristic configuration of the index value determination method according to the present invention is that in the concentration value acquisition step, a reference concentration value of acetone released from a subject who has not ingested the acetone-generating species is acquired;
In the index value determining step, a rate of increase in acetone concentration in a predetermined interval from the reference concentration value to the maximum concentration value is determined as the index value.

In each of the characteristic configurations described above, the rate of increase in acetone concentration 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 will increase as well as the blood concentration of the acetone-producing species; however, the higher the mitochondrial activity, the more , since the amount of acetoacetic acid to be processed increases, the generation of acetone due to the decomposition of acetoacetic acid is suppressed. In other words, the higher the mitochondrial activity, the lower the rate of increase in acetone concentration. Therefore, mitochondrial activity can be understood by using the rate of increase in acetone concentration as an index value.

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

In each of the above characteristic configurations, after the concentration value of acetone reaches the maximum concentration value, the minimum intake amount of the acetone-producing species that maintains the 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 amount of acetone-producing species ingested by a subject does not exceed the amount that mitochondria can process, the acetone concentration value decreases after reaching the maximum value. On the other hand, if the amount of acetone exceeds what the mitochondria can process, the concentration value of acetone will maintain the concentration value within a predetermined range for a certain period of time after reaching the maximum value. Therefore, the higher the mitochondrial activity, the higher the minimum intake of acetone generating species that will maintain the concentration value within a predetermined range for a certain period of time after the concentration value of acetone reaches the maximum concentration value. Therefore, mitochondrial activity can be understood by using the minimum intake of acetone-producing species as described above as an index value.

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 ingests nutrients together with the acetone-producing species. It is in the point where it is.
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 along with the acetone-producing species. It is in.

According to new findings discovered by the inventors of the present application, when a subject ingests nutrients together with acetone-producing species, the obtained acetone concentration value This increases reliability and enables measurements to be performed with good reproducibility. This is presumed to be due to the following reasons.

In other words, if the subject is in a fasting state at the time of measurement, or if the subject is in a state where insulin is secreted excessively due to eating a carbohydrate-rich meal, the subject may be in a hypoglycemic state. There may be cases. If the subject is in a hypoglycemic state, the ingested acetone-generating species will be used to generate energy, and the amount of acetone-generating species used to generate energy will fluctuate during measurement, causing acetone-generating Since the amount of energy generated varies accordingly, a situation may arise in which the obtained acetone concentration value varies depending on the amount of energy produced. However, if nutrients are ingested together with acetone-generating species, the intake of nutrients raises blood sugar levels and suppresses the production of energy using acetone-producing species. This is presumed to be because the acetone concentration value can be obtained in a state where the amount is less likely to fluctuate during measurement.

According to each of the above characteristic configurations, since the test subject ingests nutrients together with acetone-generating species, hypoglycemia may occur due to the test subject being hungry at the time of measurement or excessive insulin secretion. The acetone concentration in a state where the generation of energy using the ingested acetone-generating species can be suppressed, and fluctuations in the amount of acetone-generating species during measurement due to energy generation are 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.

Furthermore, the characteristic configuration of the mitochondrial activity evaluation system according to the present invention is as follows:
Any of the above index value determination systems;
and an activity evaluation means for evaluating the mitochondrial activity of the subject based on the determined index value,
The activity evaluation means compares the determined index value with past index values for the same subject to evaluate the mitochondrial activity of the subject.
Further, the characteristic configuration of the mitochondrial activity evaluation method for evaluating the mitochondrial activity of the subject using the mitochondrial activity evaluation system is as follows:
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-producing species;
an index value determination step of determining the index value that has a correlation with the mitochondrial activity of the subject, using at least the acquired acetone concentration value;
carrying out an activity evaluation step of evaluating the mitochondrial activity of the subject based on the determined index value;
In the activity evaluation step, the activity evaluation means compares the determined index value with past index values regarding the same subject to evaluate the mitochondrial activity of the subject.
Furthermore, the characteristic configuration of the mitochondrial activity evaluation method according to the present invention is as follows:
After determining the index value by any of the above index value determination methods,
Performing an activity evaluation step of evaluating the mitochondrial activity of the subject based on the determined index value,
In the activity evaluation step , based on the determined index value, the determined index value is compared with past index values regarding the same subject by an activity evaluation means for evaluating the mitochondrial activity of the subject, and the The point is to evaluate the mitochondrial activity of the subject.

In the characteristic configuration of the mitochondrial activity evaluation system and mitochondrial activity evaluation 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-producing species is continuously measured. Acquired regularly or intermittently. Then, using at least the obtained acetone concentration value, an index value that correlates with the mitochondrial activity of the subject is determined. Thereafter, this index value is compared with past index values for the same subject to evaluate the mitochondrial activity of the subject. In this way, by comparing the acquired index value with past index values for the same subject, changes in the mitochondrial activity of that subject, that is, current mitochondrial activity is higher than past mitochondrial activity. It is possible to evaluate whether the value is increasing or decreasing. By making it possible to evaluate mitochondria, we can detect lifestyle-related disease prevention groups, measure aging indicators, estimate daily calorie intake, screen for foods that affect mitochondrial activity, and verify 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 decrease in mitochondrial activity, glycolytic system and It becomes possible to measure the balance of the TCA cycle and understand the status of mitochondrial diseases.

FIG. 1 is a block diagram showing a schematic configuration of an index value determination device and a mitochondrial activity evaluation device according to the present embodiment. 1 is a flowchart showing an index value determination method and a mitochondrial activity evaluation method according to the present embodiment. It is a graph showing the relationship between the elapsed time after ingesting an acetone-producing species, the amount of increase in blood 3HB concentration, and the amount of increase in acetone concentration. It is a graph showing the relationship between the elapsed time after ingesting an acetone-producing species, the amount of increase in blood 3HB concentration, and the amount of increase in acetone concentration. It is a graph showing the relationship between the elapsed time after ingesting an acetone-producing species, the amount of increase in blood 3HB concentration, and the amount of increase in acetone concentration. It is a graph showing the relationship between the elapsed time after ingesting an acetone-producing species, the amount of increase in blood 3HB concentration, and the amount of increase in acetone concentration. It is a graph showing the relationship between the elapsed time after ingesting an acetone-producing species and the amount of change in acetone concentration. It is a graph showing the relationship between the amount of change in acetone concentration and the elapsed time after ingesting acetone-generating species and sugar.

[First embodiment]
Hereinafter, an index value determination device and a mitochondrial activity evaluation device according to a 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 acquisition section 2 (concentration value acquisition means) that acquires the concentration value of acetone, and a concentration value acquisition section 2 that acquires the concentration value of acetone. and an index value output unit 3 (index value determination means) that determines and outputs an index value that has a correlation with the mitochondrial activity of the subject. It is equipped with an activity evaluation section 5 (activity evaluation means) that evaluates the mitochondrial activity of the examiner, and an index value storage section 6 that stores index values, and the concentration value acquisition section 2 and index value output section 3 store the index values. This is a determining 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. Note that 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 section 3 determines an acetone concentration increase rate as an index value based on the concentration value received from the index value output section 3, and transmits it to the activity evaluation section 5 or an appropriately provided display device 11. Specifically, in this embodiment, the acetone-generating species is selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate ester, and acetoacetic acid, which are acetonogenic species that are ultimately decomposed in the body to generate acetone. The concentration value of acetone contained in the breath of a test subject who has ingested at least one of the acetone-producing species, and the concentration value of acetone contained in the breath of a test subject who has not ingested an acetone-producing species (reference concentration value) Based on this, the rate of increase in acetone concentration in a predetermined section from the reference concentration value to the maximum concentration value is determined as an index value. Note that 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. Note that the display device 11 may be incorporated into the mitochondrial activity evaluation device 1 or the index value determination device 4, or may be separately provided outside of these devices.

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

Next, a method for determining an index value and a method for evaluating mitochondrial activity will be described with reference to FIG. 2. First, in step #1, a reference concentration value is measured. Specifically, acetone contained in the breath of a subject who has not ingested an acetone-generating species is detected using the breath sensor 10, and an acetone concentration value (reference concentration value) is obtained. In addition, when the above-mentioned mitochondrial activity evaluation device 1 is used, the detection result by the exhaled breath sensor 10 is transmitted to the concentration value acquisition section 2 to acquire the reference concentration value of acetone, and this reference concentration value is sent to the index value output section 3. sent to.

Then, in step #2, the subject ingests the acetone-generating species. The amount of acetone-generating species ingested by the test subject shall be an appropriate amount determined for each test subject depending on their health condition, sports ability, etc., and the rate of increase in acetone concentration will be at least a predetermined speed in step #6 described below. If it is determined that this is the case, the same amount of acetone-generating species will be ingested in the future index value determination method and mitochondrial activity evaluation method for the same subject. The amount of acetone-producing species ingested 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 concentration value of acetone is measured at regular intervals (concentration value acquisition step). That is, acetone contained in the breath of a subject who has ingested an acetone-generating species is detected at regular intervals using the breath sensor 10, and the acetone concentration value is obtained. In addition, when the above-mentioned mitochondrial activity evaluation device 1 is used, the detection result by the exhaled breath sensor 10 is transmitted to the concentration value acquisition section 2 to acquire the concentration value of acetone, and this concentration value is transmitted to the index value output section 3. be done.

Next, in step #4, it is determined whether the maximum concentration value of acetone has been obtained, and if the maximum concentration value has been obtained, the process moves to step #5; if the maximum concentration value has not been obtained, the process proceeds to step #5. Then return to step #3. Specifically, if the obtained concentration value is higher than the concentration value obtained by measuring at the timing one time before this concentration value was measured, it is determined that the maximum concentration value has not been obtained; It is determined that the maximum concentration value has been obtained. When using the mitochondrial activity evaluation device 1, the index value output unit 3 determines whether the maximum concentration value of acetone has been acquired.

As step #5, the rate of increase in acetone concentration is determined as an index value (index value determination step). Specifically, the concentration value of acetone is determined based on the concentration value at a predetermined timing and elapsed time from the reference concentration value to the maximum concentration value, and the reference concentration value. 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 rate of increase in acetone concentration is calculated in the index value output section 3, the rate of increase in acetone concentration is determined as an index value, and the determined rate of increase in acetone concentration is outputted to the activity evaluation section. 5 or to the display device 11. The above-mentioned predetermined timing is, for example, the timing when the rate of increase in acetone concentration becomes constant, and in the case of using the mitochondrial activity evaluation device 1, when the rate of increase in acetone concentration becomes constant, the index is determined based on the measurement data. This is the timing determined by the value output unit 3. Note that the rate of increase in acetone concentration as the index value may be calculated based on the reference concentration value, the maximum concentration value, and the time required to reach the maximum concentration value from the reference concentration value.

These steps #1 to #5 correspond to the index value determination method, and by performing steps #1 to #5 as described above, the acetone concentration as an index value that correlates with mitochondrial activity can be determined. Since the rate of increase can be determined, it becomes possible to easily understand the mitochondrial activity of the subject from this index value without using cells or the like. The index value determined in this way is based on the relationship between the index value and the amount of acetone-producing species ingested, the sex, age, lifestyle of the subject, the presence or absence of exercise, the presence or absence of disease, etc. By creating a map, you can detect lifestyle-related disease prevention groups, measure aging indicators, estimate daily calorie intake, screen for foods that affect mitochondrial activity, verify dietary habits, and various diseases. Verification of the relationship between longevity and mitochondrial activity, Verification of the relationship between longevity and mitochondrial activity, Verification of the effects of exercise training and setting of the optimal training amount, Confirmation of mental stress based on short-term decrease in mitochondrial activity, glycolysis and TCA cycle It can also be used to measure balance and understand the status of mitochondrial diseases.

In step #6, it is determined whether the determined rate of increase in acetone concentration is greater than or equal to a predetermined rate, and if it is determined to be greater than or equal to the predetermined rate, the process proceeds to step #7. On the other hand, if it is determined that the speed is less than the predetermined speed, the process returns to step #2, increases the intake amount of acetone-generating species, and moves to step #3 again. This may be due to the possibility that the rate of increase in acetone concentration did not correlate well with the mitochondrial activity of the test subjects because the amount of acetone-producing species ingested by the test subjects was an amount that could be sufficiently processed by the mitochondria. This is because of the high

In step #7, it is determined whether or not there is a past rate of increase in acetone concentration for the same subject, and if it exists, the process moves to step #8, and if it does not, it ends. Then, in step #8, the acetone concentration increase rate determined this time is compared with the past acetone concentration increase rate for the same subject to determine whether the subject's mitochondrial activity is higher than in the past. Or evaluate whether it is low (activity evaluation step).

For these steps #6 to #8, when the mitochondrial activity evaluation device 1 is used, the activity evaluation section 5 stores the determined acetone concentration increase rate in the index value storage section 6, and also stores the determined acetone concentration increase rate in the index value storage section 6. It is determined whether or not the speed is higher than a predetermined speed (step #6), and when it is determined that the speed is higher than a predetermined speed, the past acetone concentration regarding the same subject is determined by referring to the index value storage unit 6. It is determined whether the rate of increase is stored (step #7), and if it is, the rate of increase in acetone concentration is compared with the rate of increase in past acetone concentration for the same subject. It is evaluated whether the person's mitochondrial activity is higher or lower than in the past, and the result is transmitted to the display device 11. On the other hand, if 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 rate of increase in acetone concentration as an index value of mitochondrial activity, it is possible to evaluate whether the mitochondrial activity of the same subject is higher or lower compared to past results. For example, if the rate of increase in acetone concentration is determined as an index value for each subject during regular health checkups, it will be possible to determine how 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 rate of increase in acetone concentration, which is an index value that correlates with the mitochondrial activity of the subject, and to use this rate of increase in acetone concentration. Various tests and verifications regarding mitochondrial activity can be performed. In addition, by comparing the rate of increase in acetone concentration, which is an index value, with the rate of increase in acetone concentration in the past for the same subject, it is possible to inform the subject how mitochondrial activity has changed, and to detect lifestyle-related diseases. It can provide an opportunity to work on the prevention of cancer and aging.

Hereinafter, specific experimental examples 1 to 4 will be explained.

(Experiment example 1)
When 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 exhaled acetone concentration value (increase relative to 0 minute) after 60 minutes, 90 minutes, and 120 minutes. To determine the concentration of acetone in exhaled breath, 1 L of exhaled air was collected into a collection bag at each hour and analyzed using a gas chromatograph. Because the amount of 3HB salt ingested was small relative to the mitochondrial activity of Subject A (52-year-old male), the increase in blood 3HB concentration rose to 0.2mM after 30 minutes, then decreased to 0, and The amount of increase in the acetone concentration also reached a maximum value at a low value of 0.1 ppm after 60 minutes, and then immediately decreased. If the pattern of change in the amount of increase in the acetone concentration value becomes a pattern in which the amount of increase reaches the maximum and then immediately decreases, it shall be determined that it is necessary to increase the amount of 3HB salt intake and perform the measurement again. .
Note that the rate of increase in acetone concentration per hour from 0 to 60 minutes (0.096 ppm/hr) is lower than the rate of increase in acetone concentration in Experimental Examples 2 to 4, which will be described later. If the rate 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 ingested and perform the measurement again.
Additionally, the peak increase in exhaled acetone concentration appears later than the peak increase in blood 3HB concentration because acetone generated in mitochondria is transferred to body fluids and then released from exhaled air. This is probably because it takes time.
In addition, from the body water content (64 kg x 70% = 45 L) estimated from Subject A's weight (64 kg) and the amount of 3HB salt ingested (1 g), it was determined that when the entire amount of 3HB salt ingested was transferred to body fluids, The blood 3HB concentration is 1g/104 (3HB molecular weight)/45L = 0.21mM, which is almost the same as the measured value of 0.2mM, so almost all of the ingested 3HB salt was transferred to body fluids, and this measurement It is assumed that it was used for.

(Experiment example 2)
When ingesting 3g of 3HB salt (30ml of 10% 3HB neutralized with Na:Ca:Mg=70:15:15), 0 minutes (before intake), 30 minutes, 60 minutes, 90 minutes, 120 minutes. FIG. 4 shows the relationship between the amount of increase in blood 3HB concentration (increase relative to 0 minutes) and the increase in acetone concentration value in exhaled breath (increase relative to 0 minutes) after minutes. For the acetone concentration value in exhaled breath, 1 L of exhaled breath was collected into a collection bag at each time and analyzed using a gas chromatograph. The amount of 3HB salt ingested was sufficiently large compared to the mitochondrial activity of Subject A (a 52-year-old male), so the increase in blood 3HB concentration rose to 0.4mM after 60 minutes, after which it was used by the mitochondria. It gradually decreased. The amount of increase in acetone concentration in exhaled breath rose to 0.9 ppm after 60 minutes, and then gradually decreased while remaining within a predetermined range. If the pattern of change in the amount of increase in the acetone concentration value becomes a pattern in which the amount of increase remains within a predetermined range after the amount of increase reaches the maximum, it is determined that the measurement was successful and there is no need to remeasure. shall be taken as a thing.
In this case, the index value that correlates with mitochondrial activity may be the amount of intake (3 g in this experimental example) that maintains the acetone concentration within a predetermined range after the increase in acetone concentration reaches the maximum. However, the acetone concentration increase rate per hour from 0 minutes to 60 minutes (0.798 ppm/hr) may be used. Note that the latter is a simpler and more detailed indicator.

(Experiment example 3)
When ingesting 5g of 3HB salt (50ml of 10% 3HB neutralized with Na:Ca:Mg=70:15:15), 0 minutes (before intake), 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 exhaled acetone concentration (increase relative to 0 minute) after 5 minutes. To determine the concentration of acetone in exhaled breath, 1 L of exhaled breath was collected into a collection bag at each hour and analyzed using a gas chromatograph. Because the amount of 3HB salt ingested was sufficiently large compared to the mitochondrial activity of Subject A (52-year-old male), the increase in blood 3HB concentration rose to 0.7mM after 60 minutes, and then the amount of 3HB salt was utilized by the mitochondria. It gradually decreased. Even though the amount of 3HB salt ingested is 5 times the 1g of Experimental Example 1, the maximum increase in 3HB concentration is 3.5 times because it is not possible to consume all of the ingested 3HB. This is thought to be due to the The increase in acetone concentration in exhaled breath rose to 1.1 ppm after 90 minutes, and then gradually decreased. The pattern of change in the amount of increase in the acetone concentration value is a pattern in which the amount of increase remains within a predetermined range after the amount of increase reaches the maximum, so as in the case of Experimental Example 2 above, the measurement was successful. , it is determined that there is no need to remeasure.
The rate of increase in acetone concentration per hour from 0 minutes to 60 minutes (0.756 ppm/hr) as an index value was approximately the same value as in Experimental Example 2. From this, the amount of 3HB salt ingested by the subject should be such that the amount of 3HB salt ingested by the subject is such that the pattern of increase in acetone concentration remains within a predetermined range after the amount of increase reaches its maximum. Even if there are many, there is no particular problem. Furthermore, by continuously performing measurements using a sensor element or the like that can detect acetone, it is possible to more accurately calculate the rate of increase in acetone concentration as an index value.

(Experiment example 4)
When 3g of 3HB salt was ingested (30ml of 10% 3HB neutralized with Na:Ca:Mg=70:15:15), 0 minutes (before ingestion), 30 minutes, 60 minutes, and 90 minutes later. FIG. 6 shows the relationship between the increase in blood 3HB concentration (increase relative to 0 minutes) and the increase in exhaled acetone concentration (increase relative to 0 minute). To determine the acetone concentration in exhaled breath, 1 L of exhaled breath was collected into a collection bag at each time point and analyzed using a gas chromatograph. Because the amount of 3HB ingested was sufficiently large compared to the mitochondrial activity of Subject B (59-year-old male), the increase in blood 3HB concentration rose to 0.7mM after 60 minutes, and then was used by the mitochondria and gradually decreased. did. The increase in acetone concentration in exhaled breath rose to 0.8 ppm after 30 minutes, and then gradually decreased. If the pattern of increase in acetone concentration becomes like this, the measurement is judged to be successful. The rate of increase in acetone concentration per hour from 0 minutes to 30 minutes as mitochondrial activity (1.602 ppm/hr) was approximately twice that of Subject A in Experimental Examples 2 and 3. Since Subject B was older and had lower mitochondrial activity, it is thought that the rate of acetoacetic acid utilization by the mitochondria was slower, and more acetone was generated, resulting in a faster acetone concentration rate.

[Second embodiment]
In the second embodiment, a subject who has ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyric acid ester, and acetoacetic acid, which are acetone-producing species, generates acetone. The difference from the first embodiment is that nutrients are ingested at the same time as seeds.

That is, in the second embodiment, the mitochondrial activity evaluation device 1 calculates the concentration value of acetone contained in the exhaled breath of a subject who ingested nutrients at the same time as acetone-producing species, and the concentration value of acetone in a state in which neither acetone-producing species nor nutrients were ingested. The rate of increase in acetone concentration is determined as an index value based on the concentration of acetone contained in the subject's breath (reference concentration value), and the rate of increase in acetone concentration, which is the determined index value, is determined as the index value. Assess mitochondrial activity. In addition, "nutrients" in this application are not particularly limited as long as they can be converted into glucose in the body, and include, for example, carbohydrates, carbohydrates, proteins, amino acids, lipids, dietary fibers, etc. The subject may ingest only one of these together with the acetone-generating species, or may ingest a combination of two or more.

In this way, because the test subject is ingesting nutrients at the same time as the acetone-producing species, hypoglycemia may occur due to the test subject being hungry at the time of measurement or excessive insulin secretion. The acetone concentration in a state where the generation of energy using the ingested acetone-generating species can be suppressed, and fluctuations in the amount of acetone-generating species during measurement due to energy generation are 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 accuracy of evaluation of mitochondrial activity can be improved.

Below, we will explain an experiment conducted to confirm the effect of ingesting nutrients at the same time as acetone-producing species.

A sample in which 5 g of 3HB was dissolved in 100 ml of water and adjusted to pH 4 with potassium hydroxide (sample 1), and a sample in which 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 1). Samples 1 and 2 were prepared and sample 2) were prepared respectively, and sample 1 and 2 were ingested by subject C. Before ingestion of the sample and every time a predetermined period of time elapsed after ingestion of the sample, the exhaled breath of subject C in a resting state was measured. was collected and analyzed using a gas chromatograph to measure the acetone concentration in exhaled breath. FIG. 7 is a graph showing the relationship between the elapsed time after ingesting the sample and the amount of change in the acetone concentration value (the amount of change compared to before ingestion) when Sample 1 was ingested, and FIG. It is a graph showing the relationship between the elapsed time after sample ingestion and the amount of change in the acetone concentration value (the amount of change from before ingestion) for each case. In addition, we conducted two experiments in which Sample 1 was taken in the morning (“1 in the morning” and “2 in the morning” in Figure 7), and two experiments in which Sample 1 was taken in the afternoon (“1 in the afternoon” in Figure 7). "Afternoon 2"), two experiments in which Sample 2 was taken in the morning ("AM + Nutrition 1" and "Am + Nutrition 2" in Figure 8), and two experiments in which Sample 2 was taken in the afternoon (Figure 8). A total of eight experiments ("afternoon + nutrition 1" and "afternoon + nutrition 2") were conducted on different days.

Comparing the graphs related to each experiment in the case of ingesting Sample 1, it can be seen that there is a large variation as shown in FIG. Specifically, the minimum and maximum values of the amount of change in the acetone concentration value after a predetermined period of time has passed since ingestion of Sample 1 are as follows: At 15 minutes, the minimum value is -119 ppb (2 p.m.), and the maximum value is 31 ppb (2 p.m.). 1 a.m.), and after 30 minutes, the minimum value is -37 ppb (2 a.m.), the maximum value is 26 ppb (1 a.m.), and after 45 minutes, the minimum value is -35 ppb (1 p.m.). The maximum value was 223 ppb (2 a.m.), and after 60 minutes, the minimum value was 93 ppb (1 a.m.) and the maximum value was 287 ppb (2 a.m.).

On the other hand, when comparing the graphs related to each experiment in the case of ingesting Sample 2, it can be seen that the variation is smaller than in the case of ingesting Sample 1, as shown in FIG. Specifically, the minimum and maximum values of the amount of change in the acetone concentration value after a predetermined period of time has passed since ingestion of Sample 2 are as follows: At 15 minutes, the minimum value is 19 ppb (AM + Nutrition 1), and the maximum value is 75 ppb. (afternoon + nutrition 2), and after 30 minutes, the minimum value is 86 ppb (am + nutrition 1), the maximum value is 196 ppb (afternoon + nutrition 2), and after 45 minutes, the minimum value is 234ppb (AM + Nutrition 1), maximum value is 302ppb (AM + Nutrition 2), and after 60 minutes, the minimum value is 355ppb (PM + Nutrition 2), and the maximum value is 539ppb (AM + Nutrition 2). there were.

In this way, the reason for the change in the degree of dispersion between when sugar was ingested at the same time as 3HB and when it was not ingested is that when sugar was not ingested at the same time as 3HB, at the time of measurement, the subject When a person is in a fasting state or when insulin is secreted excessively due to eating a high-carbohydrate meal, a state of hypoglycemia occurs, and the ingested 3HB is used to generate energy. As the amount of 3HB used for generation changes during measurement, the amount of acetone generated also changes accordingly, and as a result, the obtained acetone concentration value changes depending on the amount of energy generated. However, when sugar is ingested at the same time as 3HB, the sugar intake raises blood sugar levels and suppresses the production of energy using 3HB. It is assumed that the acetone concentration value was obtained while the amount was less likely to fluctuate during measurement, and the variation was reduced.

[Another embodiment]
[1] In the above embodiment, an aspect is shown in which the rate of increase in acetone concentration is used as an index value, but the present invention is not limited to this. As an index value that correlates with mitochondrial activity, instead of the rate of increase in acetone concentration, an acetone generating species that maintains the concentration value within a predetermined range for a certain period of time after the acetone concentration value reaches the maximum concentration value. The minimum intake amount 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 concentration value, preferably ±20% of the maximum concentration value. . If the amount of acetone-producing species ingested by the subject does not exceed the amount that mitochondria can process, the concentration of acetone will reach a maximum value and then decrease, whereas the amount that mitochondria can process will decrease. If the amount is exceeded, the concentration value of acetone will maintain the concentration value within a predetermined range for a certain period of time after reaching the maximum value. Therefore, the higher the mitochondrial activity, the higher the minimum intake of acetone generating species that will maintain the concentration value within a predetermined range for a certain period of time after the concentration value of acetone reaches the maximum concentration value. Therefore, mitochondrial activity can be understood using the minimum intake of acetone-producing species as described above as an index value.

[2] In the above embodiment, the acetone contained in the exhaled breath of the subject is detected at fixed time intervals, that is, intermittently using the breath sensor, but this is not limited to this. Acetone may be continuously detected. Further, the sensor for detecting acetone is not limited to an exhalation 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 index value is transmitted from the activity evaluation unit 5 to the index value storage unit 6 and stored, but the present invention is not limited to this, and the index value is transmitted from the index value output unit to the index value storage unit 6. The index value may be sent to the unit and stored therein, or an appropriate storage unit may be provided to store the density value acquired by the density value acquisition unit.

[4] In the above embodiment, the index value output unit 3 determines and outputs the rate of increase in acetone concentration as the index value, but it is not necessarily necessary to output the index value, and the index value may be stored. Alternatively, the activation evaluation section may access and acquire the information as appropriate.

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

[6] In the second embodiment, the subject ingests nutrients at the same time as the acetone-producing species, but the subject is not limited to this. Nutrients may be ingested after ingesting the outbreak species.

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 a mitochondrial activity evaluation system and a mitochondrial activity evaluation system capable of easily evaluating mitochondrial activity based on the index value. It can be used for mitochondrial activity evaluation method.

1 Mitochondrial activity evaluation device (mitochondrial activity evaluation system)
2 Concentration value acquisition unit (concentration value acquisition means)
3 Index value output section (index value determining means)
4 Index value determination device (index value determination system)
5 Activity evaluation section (activity evaluation means)

Claims (12)

A subject who ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate ester, and acetoacetic acid, which are acetone-generating species that are ultimately decomposed in the body to generate acetone. Concentration value acquisition means that continuously or intermittently acquires the concentration value of the acetone released from the
An index value determining system, comprising: 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. The concentration value acquisition means acquires a reference concentration value of acetone released from a subject who has not ingested the acetone-generating species;
2. The index value determining system according to claim 1, wherein the index value determining means determines, as the index value, a rate of increase in acetone concentration in a predetermined interval from the reference concentration value to the maximum concentration value of the acetone. In the index value determination means, after the concentration value of the acetone reaches the maximum concentration value, the minimum intake amount of the acetone-producing species is set as the index value so that the concentration value is maintained within a predetermined range for a certain period of time. The index value determination system according to claim 1, wherein the index value determination system determines an index value. The index value determination according to any one of claims 1 to 3, wherein the subject who has ingested at least one selected from the acetone-producing species ingests nutrients along with the acetone-producing species. system. The index value determination system according to any one of claims 1 to 4,
and an activity evaluation means for evaluating the mitochondrial activity of the subject based on the determined index value,
A mitochondrial activity evaluation system, wherein the activity evaluation means compares the determined index value with a past index value regarding the same subject to evaluate the mitochondrial activity of the subject. A method for determining an index value correlated with the mitochondrial activity of the subject using the index value determination system according to any one of claims 1 to 4, comprising:
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-producing species;
an index value determination 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 the 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-producing species;
an index value determination step of determining the index value that has a correlation with the mitochondrial activity of the subject, using at least the acquired acetone concentration value;
carrying out an activity evaluation step of evaluating the mitochondrial activity of the subject based on the determined index value;
In the activity evaluation step, the activity evaluation means compares the determined index value with a past index value regarding the same subject, and evaluates the mitochondrial activity of the subject. A subject who ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyrate ester, and acetoacetic acid, which are acetone-generating species that are ultimately decomposed in the body to generate acetone. a concentration value acquisition step of continuously or intermittently acquiring the concentration value of the acetone released from the
an index value determination 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 acquisition step, a reference concentration value of acetone released from a subject who has not ingested the acetone-generating species is acquired;
9. The index value determination method according to claim 8, wherein, in the index value determination step, a rate of increase in acetone concentration in a predetermined interval from the reference concentration value to the maximum concentration value is determined as the index value. In the index value determining step, the index value is a minimum intake amount of the acetone-producing species that maintains the concentration value within a predetermined range for a certain period of time after the concentration value of acetone reaches the maximum concentration value. The method for determining an index value according to claim 8. 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 has ingested nutrients along 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,
Performing an activity evaluation step of evaluating the mitochondrial activity of the subject based on the determined index value,
In the activity evaluation step , based on the determined index value, the determined index value is compared with past index values regarding the same subject by an activity evaluation means for evaluating the mitochondrial activity of the subject, and the A mitochondrial activity evaluation method for evaluating the mitochondrial activity of a subject.

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