JP7379767B2 - Non-invasive method for estimating serum zinc levels - Google Patents

Description

The present invention relates to a method for non-invasively estimating a serum zinc level using a subject's age, urinary zinc level, and urinary uric acid level as indicators.

Zinc is an essential trace element, and its deficiency causes zinc deficiency diseases such as growth disorders, hair loss, taste abnormalities, skin disorders, sexual dysfunction, immunodeficiency, decreased appetite, and delayed wound healing. Approximately 1.5 to 3 g of zinc exists in a normal weight human body, and most of it is bound to proteins and distributed in skeletal muscles, bones, skin, liver, brain, kidneys, hair, etc.

In Japan, recommended intake levels and tolerable upper limits for zinc have been established, but it has been pointed out that it is difficult to determine the nutritional status of zinc, especially as there are no specific indicators of deficiency status. As an indicator of zinc nutritional status, a common method is to collect blood from a subject and measure the serum zinc level. However, blood sampling is invasive, which places a heavy burden on the subject, and a non-invasive method for measuring serum zinc levels is required.

One method of non-invasively evaluating the nutritional status of zinc is to use the amount of zinc excreted into the urine as an index. However, in healthy people, the amount of zinc excreted in the urine is very low at about 0.5 mg/day, and in subjects with diseases such as hypoalbuminemia, the binding mode of zinc in serum changes. As a result, the amount of zinc excreted in the urine increases, and there is a risk that the nutritional status of people with true zinc deficiency may be misdiagnosed as normal. Another method is to measure the zinc concentration in hair, but hair is easily affected by external influences, and the zinc concentration in hair increases markedly, especially when hair conditioners or shampoos containing zinc are used. , its interpretation becomes difficult.

Although there is a method of estimating serum zinc levels from the results of a meal frequency survey, the present inventors have found that there is no correlation between the zinc intake estimated from the results of a meal frequency survey and the serum zinc level. This also agrees with the report in Non-Patent Document 1.

Patent Document 1 (Japanese Unexamined Patent Publication No. 2017-83340) discloses blood test values of hemoglobin concentration, hematocrit, albumin concentration, total cholesterol concentration, neutral fat concentration, sodium ion concentration, and chloride ion concentration, which are general blood test items. In combination, we are proposing a device for estimating zinc deficiency status. This is an excellent technique that reduces the physical burden on the subject in that there is no need to additionally draw blood for serum zinc levels, which are not included in general blood tests. However, this method requires general blood test values, making it difficult for subjects to casually check for zinc deficiency on a daily basis, and a simpler method is required.

JP2017-83340A

Janet C king, “Yet Again, Serum Zinc Concentrations Are Unrelated to Zinc Intakes”, The Journal of Nutrition, 2018, 148(9), 1399-1401

The purpose of the present invention is to provide a non-invasive method for estimating serum zinc levels.

The main configuration of the present invention is as follows.
1. A method of estimating the serum zinc level using any two or more of the subject's age, urinary zinc level, and urinary uric acid level as indicators.
2. A method to estimate serum zinc level using the subject's age, urinary zinc level, and urinary uric acid level as indicators.
3.1.2. A system for estimating a serum zinc level using the method for estimating a serum zinc level according to any one of the above, and providing an oral composition for supplementing a zinc deficiency to a subject.

The present invention is a method for non-invasively estimating a serum zinc level using any two or more of a subject's age, urinary zinc level, and urinary uric acid level as indicators. The target person (customer) collects a urine sample using a simple method such as a urine collection kit at a store or at home, and sends it by mail along with information including the target person's age, to check their own serum zinc level and zinc concentration. It becomes possible to know the state of sufficiency. In addition, subjects who are deficient in zinc can be provided with oral compositions such as supplements and drinks that allow them to efficiently ingest zinc in addition to their daily meals. Furthermore, since the present invention does not require blood sampling and places an extremely low burden on the subject, even after a certain period of time after the subject has ingested the oral composition, the subject can easily re-examine the progress after ingestion.

Correlation diagram between serum zinc value and serum zinc value estimated from estimation formula 1-1.

The present inventors have discovered that the serum zinc level can be estimated with high accuracy by using any two or more of the subject's age, urinary zinc level, and urinary uric acid level as indicators.
Measure the urinary zinc concentration [μg/dL], uric acid concentration [mg/dL], and creatinine (Cre) concentration [g/mL], and calculate the urinary zinc value [μg/g Cre] and urinary uric acid value from these. [mg/g Cre] was calculated. In addition, the concentration of urinary components is easily influenced by diet, water intake, sweating, etc., and the concentration of the components varies greatly depending on the concentration of urine. Therefore, the urinary zinc level and urinary uric acid level are based on the creatinine value measured at the same time. This is the value after creatinine correction to find the ratio.

As a method for estimating the serum zinc level from any two or more of the subject's age, urinary zinc level, and urinary uric acid level, an estimation formula derived by regression analysis can be used, and this estimation formula is as follows: It can be a linear expression, polynomial, logarithmic expression, exponential expression, etc. As an example, the following estimation formulas 1 to 4 are given.

(Estimation formula 1)
Estimated serum zinc level [μg/dL] = (α1) × urinary zinc level [μg/g Cre]
-(β1)×urinary uric acid level [mg/g Cre]
-(γ1)×age
+(δ1)
(α1) is preferably 0.006 to 0.014, more preferably 0.008 to 0.012. (β1) is preferably 0.008 to 0.016, more preferably 0.010 to 0.014. (γ1) is preferably 0.09 to 0.17, more preferably 0.11 to 0.15. (δ1) is preferably 70 to 100, more preferably 75 to 95.

(Estimation formula 2)
Estimated serum zinc level [μg/dL] = (α2) × urinary zinc level [μg/g Cre]
-(γ2)×age
+(δ2)
(α2) is preferably 0.006 to 0.014, more preferably 0.008 to 0.012. (γ2) is preferably 0.11 to 0.19, more preferably 0.13 to 0.17. (δ2) is preferably 65 to 95, more preferably 70 to 90.

(Estimation formula 3)
Estimated serum zinc level [μg/dL] = - (β2) × urinary uric acid level [mg/g Cre]
-(γ3)×age
+(δ3)
(β2) is preferably 0.006 to 0.014, more preferably 0.008 to 0.012. (γ3) is preferably 0.09 to 0.17, more preferably 0.11 to 0.15. (δ3) is preferably 75 to 105, more preferably 80 to 100.

(Estimation formula 4)
Estimated serum zinc level [μg/dL] = (α3) × urinary zinc level [μg/g Cre]
-(β3)×urinary uric acid level [mg/g Cre]
+(δ4)
(α3) is preferably 0.006 to 0.014, more preferably 0.008 to 0.012. (β3) is preferably 0.010 to 0.018, more preferably 0.012 to 0.016. (δ4) is preferably 65 to 95, more preferably 70 to 90.

Based on the above estimation formulas 1 to 4, the subject's serum zinc level can be estimated using any two or more of the subject's age, urinary zinc level, and urinary uric acid level as indicators. As the estimation formula, estimation formulas 1, 2, and 4 that include the urinary zinc value as an index are more preferable. Regarding the status of zinc sufficiency, the "Clinical Guidelines for Zinc Deficiency 2018" (Japan Society of Clinical Nutrition) states that serum zinc levels should preferably be measured early in the morning on an empty stomach, and even if the serum zinc level is less than 60 μg/dL. There are guidelines for diagnosing zinc deficiency if it is less than 60 to 80 μg/dL, and latent zinc deficiency if it is less than 60 to 80 μg/dL. In other words, if the estimated serum zinc level is 80 μg/dL or more, it is highly likely that the person is in a sufficient state. A subject's serum zinc level can be estimated and an oral composition for replenishing zinc sufficiency and/or zinc deficiency can be provided to the subject.

In the present invention, the timing of collecting urine is not particularly limited, but it is preferable to collect urine before the first meal of the day, and the first urine is collected immediately after waking up (early morning). Urine is particularly preferred.

The urine collection container used in the present invention is not particularly limited and can be used with any shape and material that does not cause deterioration of urine components used for urine tests conducted at hospitals, testing institutions, etc.

The oral composition provided by the present invention can be used for pharmaceuticals (including quasi-drugs), nutritional supplements, functional foods, foods for specified health uses, foods with functional claims, foods for patients, and other functional foods. It can be used as food and food additives. In order to facilitate continuous ingestion, it is preferably in the form of, for example, a tablet, capsule, granule, powder, pill, chewable tablet, orally disintegrating tablet, drink, or jelly. It may be a food processed into a rod shape, a plate shape, a gummy shape, or a food added to a general food form. Among these, tablet and capsule forms are particularly preferred from the standpoint of ease of ingestion. A formulation having such a dosage form can be prepared by a conventional method, and may be an immediate-release or sustained-release formulation with controlled release of zinc.

Zinc to be added to the oral composition of the present invention is not particularly limited as long as it is distributed as a food raw material for supplementing zinc. Preferred examples include zinc gluconate, zinc yeast, zinc sulfate, zinc chloride, zinc oxide, and zinc stearate, and at least one kind or a combination of two or more kinds selected from these groups can be used. can.

In addition to zinc, the oral composition provided by the present invention can contain auxiliary ingredients for increasing the bioavailability of zinc, such as vitamins, minerals, amino acids, sugars, polypeptides, and fish oil. Nutrients such as these can be added.

<Clinical test method>
A background survey (gender, date of birth, dietary intake questionnaire) was conducted on 316 Japanese men and women (156 men and 160 women) aged 20 to under 70, and urinary zinc, uric acid, and creatinine (Cre) were investigated. ) and the serum zinc concentration were measured.
The following exclusion criteria were established.
1) Those with a serious medical history or history of gastrointestinal resection surgery (excluding appendectomy)
2) Those who are pregnant or breastfeeding 3) Those who drink a lot of alcohol or smoke excessively 4) Those who are judged to be inappropriate to participate in this study by the study director

As an ethical consideration, the suitability of conducting this study was reviewed by the Ethics Review Committee, and the purpose of the study was fully explained to all subjects before conducting this clinical study. Written informed consent to participate was obtained from the participants. The subjects collected their first urine on the day of their visit, and underwent a blood test at the hospital on the morning of their visit.

(Urine collection)
Subjects were asked to collect the first urine of the early morning on the day of their visit (urine immediately after waking up) into a 10 mL urine collection container.

(Quantification of urine components)
Urinary zinc concentration was measured using Metallo Assay Zinc Measurement LS (manufactured by Metallogenics Co., Ltd.), urinary uric acid concentration was measured using "Serotec" UA-CL (manufactured by Serotec Co., Ltd.), and urinary Cre concentration was measured using "Serotec" CRE-. Automatic analysis was performed using Clinarizer (JCA-BM6070) (manufactured by JEOL Ltd.) using S (manufactured by Serotec Co., Ltd.). From the analysis, the urinary zinc concentration [μg/dL], uric acid concentration [mg/dL], and Cre concentration [mg/dL] were obtained, and the urinary zinc level [μg/g Cre] and urinary uric acid level [mg/dL] were obtained. g Cre] was calculated.

<Method for measuring serum zinc level>
The serum zinc value was analyzed using an atomic absorption spectrophotometer 240FSAA (manufactured by Agilent Technologies), and the serum zinc value (μg/dL) was obtained from the analysis results.

(Correlation coefficient and estimation formula)
Correlation coefficients and estimation formulas were obtained through regression analysis.
The following estimation formula 1-1 was obtained from the obtained urinary zinc value [μg/g Cre], urinary uric acid value [mg/g Cre], and age.
(Estimation formula 1-1)
Estimated serum zinc level [μg/dL] = 0.0104873 x urinary zinc level [μg/g Cre]
-0.012067×urinary uric acid level [mg/g Cre]
-0.132999×age
+86.183098

The following estimation formula 2-1 was obtained from the obtained urinary zinc value [μg/g Cre] and age.
(Estimation formula 2-1)
Estimated serum zinc level [μg/dL] = 0.0095 × urinary zinc level [μg/g Cre]
-0.150558×age
+82.349618

From the obtained urinary uric acid value [mg/g Cre] and age, the following estimation formula 3-1 was obtained.
(Estimation formula 3-1)
Estimated serum zinc level [μg/dL] = -0.010104×urinary uric acid level [mg/g Cre]
-0.1261×age
+89.264906

From the obtained urinary zinc value [μg/g Cre] and urinary uric acid value [mg/g Cre], the following estimation formula 4-1 was obtained.
(Estimation formula 4-1)
Estimated serum zinc level [μg/dL] = 0.0099984×urinary zinc level [μg/g Cre]
-0.014542×urinary uric acid level [mg/g Cre]
+81.480279

(result)
Table 1 shows the correlation coefficient between the serum zinc level and the age, urinary zinc level, urinary uric acid level, and serum zinc level estimated using estimation formulas 1-1 to 4-1.

No correlation was observed between serum zinc levels and age, urinary zinc levels, or urinary uric acid levels.
A correlation was observed between the serum zinc value and the serum zinc value estimated from Estimation Formulas 1-1 to 4-1, and Estimation Formulas 1-1, 2-1, and 4-1 that included urinary zinc value as an index. A high correlation was observed between the serum zinc value estimated from the above equation, and the highest correlation was observed between the serum zinc value estimated from Equation 1-1, which uses age, urinary zinc level, and urinary uric acid level as indicators. Figure 1 shows the correlation between the serum zinc level and the serum zinc level estimated from Estimation Formula 1-1.

Claims (2)

A method of estimating the serum zinc level based on any of the following estimation formulas 1 to 4, using any two or more of the subject's age, urinary zinc level, and urinary uric acid level as indicators.
(Estimation formula 1)
Estimated serum zinc level [μg/dL] = (α1) × urinary zinc level [μg/g Cre]
-(β1)×urinary uric acid level [mg/g Cre]
-(γ1)×age
+(δ1)
[(α1) is 0.006 to 0.014, (β1) is 0.008 to 0.016, (γ1) is 0.09 to 0.17, (δ1) is 70 to 100]
(Estimation formula 2)
Estimated serum zinc level [μg/dL] = (α2) × urinary zinc level [μg/g Cre]
-(γ2)×age
+(δ2)
[(α2) is 0.006 to 0.014, (γ2) is 0.11 to 0.19, (δ2) is 65 to 95]
(Estimation formula 3)
Estimated serum zinc level [μg/dL] = - (β2) × urinary uric acid level [mg/g Cre]
-(γ3)×age
+(δ3)
[(β2) is 0.006 to 0.014, (γ3) is 0.09 to 0.17, (δ3) is 75 to 105]
(Estimation formula 4)
Estimated serum zinc level [μg/dL] = (α3) × urinary zinc level [μg/g Cre]
-(β3)×urinary uric acid level [mg/g Cre]
+(δ4)
[(α3) is 0.006 to 0.014, (β3) is 0.010 to 0.018, (δ4) is 65 to 95] A system for estimating a serum zinc level using the method for estimating a serum zinc level according to claim 1 and providing an oral composition for supplementing a zinc deficiency to a subject.