Received: 29 April 2020

| Revised: 24 August 2020 | Accepted: 27 August 2020

DOI: 10.1002/jgf2.377

ORIGINAL ARTICLE

Serum zinc concentrations and characteristics of zinc
deficiency/marginal deficiency among Japanese subjects
Hirohide Yokokawa MD, PhD| Hiroshi Fukuda MD, PhD | Mizue Saita MD, PhD |Taiju Miyagami MD, PhD | Yuichi Takahashi MD, PhD | Teruhiko Hisaoka MD, PhD |Toshio Naito MD, PhD
Department of General Medicine, Juntendo
University School of Medicine, Tokyo, Japan
Correspondence
Hirohide Yokokawa, MD, PhD, Departmentof General Medicine, Juntendo University
School of Medicine, 2-1-1 Hongo, Bunkyoku, Tokyo 113-8421, Japan.
Email: yokokawa@pa3.so-net.ne.jp

Abstract
Background: Studies that have examined serum zinc deficiency/marginal deficiency
in developed countries, including Japan, are still limited. The aim of this study wasto assess serum zinc concentrations and associated characteristics among Japanese
subjects.
Methods: This cross-sectional study, conducted from September 2016 to December
2018, included 2056 eligible subjects who participated in a voluntary health checkup.
Serum zinc concentration categories were defined as deficiency (<60 μg/dL), marginal
deficiency (≥60 to <80 μg/dL), and normal (≥80 μg/dL). Serum zinc concentrations
were compared between the first age category (<40 years) and other age categories
with Dunnett's method. Trends in P-values were estimated using the JonckheereTerpstra test for continuous variables.
Results: The proportions of subjects with deficiency and marginal deficiency were0.4% and 46.0% in men, and 0.6% and 38.4% in women, respectively. The deficiency/
marginal deficiency group had significantly lower lipid profiles and nutritional status,
and a significantly lower proportion were non–daily drinkers in both genders. Olderage was significantly associated with lower serum zinc concentration only in men.
Conclusions: Our findings clarified a high proportion of serum zinc deficiency/marginal deficiency, especially in men, and suggest a possible association between serum
zinc levels and nutritional status and alcohol consumption. It may be necessary to
manage nutritional status, including zinc intake.
KEYWORDS

aging, deficiency, epidemiology, nutrition, prevention, zinc

1 | I NTRO D U C TI O N

immunological, and clinical functions.1 Mild zinc deficiency may
cause impaired taste and smell, reduced immunity, and an increased

Zinc is a nutritionally essential trace mineral that is required for therisk of pneumonia, 2-3 and severe zinc deficiency may be associatedactivity of more than 200 enzymes involved in most major metabolicwith skin disorders, impaired vision, decreased lymphocyte function,

pathways. As such, zinc is necessary for a wide range of biochemical,

diarrhea, and anorexia.4

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,provided the original work is properly cited.
© 2020 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association
J. Gen. Fam. Med.. 2020;00:1–8.	﻿

wileyonlinelibrary.com/journal/jgf2

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YOKOKAWA et al.

Zinc deficiency is a major global health issue that affects young
children, pregnant women,

5-6

7

Although serum zinc concentration may not be a reliable indi-

and the elderly. Although this issue

cator of zinc status of an individual, it is widely used and available

has received considerable attention in developing countries because

indicator to assess the risk of zinc deficiency.9 Therefore, serumof the relationship of zinc concentrations with the risk of malnutri-zinc concentration was measured to assess zinc deficiency in thetion,8 zinc deficiency may be also observed in people in developed

study.

7,9

countries.

Total protein (g/dL; TP), albumin (g/dL; Alb), hemoglobin (g/dL),

However, studies that have examined serum zinc deficiency/

and high-sensitivity C-reactive protein (mg/dL; hs CRP) levels, andmarginal deficiency in developed countries, including Japan, are still

serum uric acid (SUA) (mg/dL) were measured. Estimated glomerular

limited. Therefore, surveys to assess the zinc deficiency are strongly

filtration rate (eGFR) was calculated using the Japanese GFR equa-

required. The present study aimed to assess serum zinc concentra-

tion: eGFR (mL/min/1.73 m2) = 194 × Cr−1.094 × age−0.287.

tions and examine the association of serum zinc deficiency/marginal

Participants were asked to complete a self-administered ques-

deficiency and other characteristics among Japanese participants

tionnaire that addressed healthy lifestyle characteristics based

who underwent regular health checkups.

on Breslow's 7 health practices.12-13 Healthy lifestyle items in thequestionnaire included non–daily alcohol consumption (alcohol con-

2 | S U B J EC T S A N D M E TH O DS

sumption 6 or less days per week), non–smoker status, exercise frequency ≥2 times per week, BMI of 18.5-24.9 kg/m2, adequate sleep
duration (7 ~ 8 hours), daily breakfast consumption, and no snacking

This cross-sectional study screened 5132 Japanese adults who par-between meals.12-13

ticipated in a voluntary health checkup in one Hospital in Tokyo,

From the self-administered questionnaire, we also collected

Japan, from September 2016 to November 2018. Of these partici-

information on medical history of comorbidities, such as diabetes

pants, 2883 were excluded because of duplicate cases who received

mellitus, dyslipidemia, hyperuricemia/gout, hypertension, cardiovas-

health checkup more than 2 times during the study period, and 193

cular disease, and cerebrovascular disease. If participants indicatedwere excluded because of missing data on serum zinc concentra-

they had any of these comorbidities, the findings were recorded astions. As a result, 2056 participants were included in the study. The

being present.

Ethics Committee of Juntendo University reviewed and approved
the research protocol using the retrospective data (No 18-296), andwritten comprehensive informed consent was obtained from all par-2.2 | Statistical analysis

ticipants when they received health checkup.
Results are presented as mean ± standard deviation (SD) for con-

2.1 | Variables

tinuous variables or prevalence (%) for categorical variables. Serumzinc concentration categories were defined following criteria basedon the treatment guidelines of zinc deficiency published by The

Blood samples were collected overnight fast. Serum concentra-

Japanese Society of Clinical Nutrition: deficiency (<60 µg/dL), mar-tions of total cholesterol (mg/dL; T-Cho), high-density lipoprotein

ginal deficiency (≥60 to <80 µg/dL), and normal (≥80 µg/dL).14 For thecholesterol (mg/dL; HDL-C), low-density lipoprotein cholesterol

statistical analysis, “deficiency/marginal deficiency” was combined(mg/dL; LDL-C), and triglycerides (mg/dL; TG) were also measured.

into a single category of zinc levels <80 μg/dL, because the propor-

LDL-C was estimated using the Friedewald equation [(TC) − (HDL-tion of subjects with deficiency (<60 μg/dL) was very small (<1.0%).

C) − (TG/5)].10 Hemoglobin A1c (HbA1c; National Glycohemoglobin

We used Student's t test for continuous variables and the chi-Standardization Program) was determined by high-performancesquared test for categorical variables for comparisons between

liquid chromatography using an automated analyzer. As for collec-

groups.

tion of blood sample, a new specific blood collection tube was used

In the study, the proportion of participants aged less thanto prevent contamination. Serum zinc concentration (μg/dL) was

40 years was 7.1%. Therefore, we made a category aged less than

measured by colorimetric method using a colorimetric reagent kit

40 years. Among participants aged 40 years or over, we divided“ACCURAS AUTO Zn” (SHINO-TEST Corporation) for determina-

into 10 years' category because The Japanese National Health andtion of zinc in serum. The reagent was applicable to all auto-analyzer

Nutrition Survey (2017) showed 10 years' age-stratified zinc in-

and widely used in Japanese hospital laboratory, without any serum

takes.15 Serum zinc levels were compared between the first age cat-

pretreatment. With-run and between-run precisions (C.V.) were 0.7-

egory (<40 years) and other 10 years' age categories with Dunnett's

1.0% and 1.4-1.9, respectively. The calibration curve was linear up

method. Trends in P-values were estimated using the Jonckheere-to 500 µg/dL, and the detection limit was 4 µg/dL. A good correla-

Terpstra test for serum zinc.

tion between the method and those of atomic absorption spectro-

Multivariable regression analysis was performed to estimate thephotometry was already reported (r = .996).11 As for the laboratory

factors associated with serum zinc deficiency/ marginal deficiency

control, “NIST (SRM3168)” (Shino-Test Corporation) was used asamong TP (g/dL), Alb (g/dL), Hb (g/dL), T-Cho (mg/dL), LDL-C (mg/reference material.

dL), TG (mg/dL), eGFR (mL/min/1.73 m2), and alcohol consumption

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YOKOKAWA et al.

status, which were significantly different between normal and serum(OR = 14.96, 95% CI = 7.09-31.57, P < .01), and TG (OR = 1.01, 95%

zinc deficiency/marginal deficiency in both genders.

CI = 1.00-1.01, P = .02) were significantly associated with serum zinc

P < .05 was considered statistically significant. All statistical

deficiency/marginal deficiency.

analyses were performed using the Statistical Package for Social
Sciences, version 22 (SPSS Inc., Chicago, IL, USA).

4 | D I S CU S S I O N

3 | R E S U LT S

Our cross-sectional study revealed a high proportion of zinc deficiency/marginal deficiency, with significantly more men experienc-

The proportions of subjects with zinc deficiency (<60 μg/dL) anding this deficiency than women (46.4% vs 39.0%, P < .01). Older age

marginal zinc deficiency (≥60 to <80 μg/dL) were 0.4% and 46.0% in

showed a negative association with serum zinc levels only in men.

men, and 0.6% and 38.4% in women, respectively (Figure 1). Among

The deficiency/marginal deficiency group had significantly lower TC,

10 participants with zinc deficiency, 5 were men (50.0%). Mean (SD)LDL-C, TG TP, Alb, and Hb measurements, and proportion of non–age, BMI, and serum zinc concentration were 63.8 (14.0) years old,daily drinker in both genders. To our knowledge, only a few studies

19.7 (1.3), and 56.7 (3.0) μg/dL, respectively.

have investigated serum zinc levels and examined the characteristics

Mean age (SD) was 61.9 (13.1) years in the deficiency/marginal de-of serum zinc deficiency/marginal deficiency in a Japanese popula-

ficiency group and 59.3 (12.8) years in the normal group. The propor-

tion. Thus, the present study offers a novel insight on this matter.

tion of men was 61.3% in the deficiency/mariginal deficiency group

Our results clarified that about 40% of those who received

and 53.8% in the normal group (Table 1). The deficiency/marginal de-voluntary health checkups were likely to experience serum zincficiency group had significantly higher mean Hs CRP measurements,

deficiency/marginal deficiency. Marginal deficiency may lead toproportion using antihypertensive medication, and a history of heart

endocrinological effects such as stunted or delayed puberty in ad-disease, and significantly lower HbA1c, T-Cho, LDL-C, TG, TP, Alb,

olescents, dermatitis, reduced appetite, mental lethargy, and taste

and eGFR measurements, and proportion of non–daily drinkers.

and smell dysfunction.16-17 Also, a Japanese cross-sectional study

Table 2 shows gender-specific characteristics. Although mean

reported the favorable association between the serum Zn/Cu ratio

age was significantly higher in the deficiency/marginal deficiency

and renal function in all subject and glycemic control in patients withgroup than the normal group in men, no significant differences weretype 2 diabetes.18 Furthermore, marginal zinc deficiency (<70 μg/

observed in women. The deficiency/marginal deficiency group haddL) may cause taste disorders among Japanese adults.19 Based on

significantly lower T-Cho, LDL-C, TG, TP, Alb, Hb, and proportion ofthis evidence, The Japanese Society of Clinical Nutrition estab-non–daily drinker in both genders.

lished treatment guidelines for zinc deficiency in 2018 and rec-Men in the higher age categories (≥50 years) were significantly

ommended a cutoff value of serum zinc concentrations <60 μg/dL

more likely to have lower serum zinc concentration compared withto represent deficiency and values ≥60 to <80 μg/dL to represent

those <40 years (Figure 2A). However, there was no relationshipmarginal deficiency.14 The Biomarkers of Nutrition for Development

between age categories and serum zinc concentrations in women

Zinc Expert Panel and the International Zinc Nutrition Consultative(Figure 2B).

Group suggest lower cutoffs for serum zinc as follows: females aged

Results of multivariable regression analysis showed that non–

≥10 years, morning/fasting, 70 µg/dL; morning/nonfasting, 66 µg/

daily alcohol consumption (OR [odds ratio] = 1.39, 95% CI [confidencedL; and afternoon, 59 µg/dL; and males aged ≥10 years, morning/interval] = 1.05-1.84, P = .02), Hb (OR = 1.16, 95% CI = 1.02-1.31,

fasting, 74 µg/dL; morning/nonfasting, 70 µg/dL; and afternoon,

P = .03), Alb (OR = 12.49, 95% CI = 6.69-23.32, P < .01), and eGFR

61 µg/dL. 20 However, a few studies have estimated serum zinc

(OR = 1.01, 95% CI = 1.00-1.02, P = .04) were significantly associ-concentrations or examined the presence of zinc deficiency/mar-ated with serum zinc deficiency/marginal deficiency in men. Among

ginal deficiency. An epidemiological study conducted among el-

women, non–daily alcohol consumption (OR = 1.62, 95% CI = 1.07-

derly Japanese people in a rural area showed that the percentage

2.46, P = .02), Hb (OR = 1.17, 95% CI = 1.00-1.36, P = .04), Albwith low serum zinc (2.5th percentile of Americans) was 37.9% in

Proportion of zinc concentrations
0.4%
Men

53.6%

Serum Zinc (mg/dl)

46.0%

~59

60~79

0.6%

80~
61.0%

Women

F I G U R E 1 Proportion of zincconcentrations

38.4%
P<0.01

0%

20%

40%

60%

80%

100%

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YOKOKAWA et al.

TA B L E 1

Participant characteristics (N = 2056)
Mean (SD) or N (%)
Serum zinc concentration (μg/dL)<80 (n = 889)

≥80 (n = 1167)P

Age (years)

61.9(13.1)

59.3(12.8)<.01

Gender (men)545(61.3%)

628(53.8%)<.01

Body mass index (kg/m2)

23.3

(3.6)

23.4

(3.6)

.41

Waist circumference (cm)83.1

(10.0)

83.6(10.0).27

Anthropometric measurements

Healthy lifestyle characteristics
Alcohol consumption (non–daily drinker)

539(64.6%)

800(73.6%)<.01

Smoking behavior (nonsmoker)

731(87.4%)

937(86.5%).55234(30.3%)

318(30.9%).80

Exercise frequency (≥2 times per week)2

Body mass index (18.5-24.9 kg/m )566(63.7%)

745(63.8%).96

Adequate sleep duration (yes)631(77.8%)

808(77.0%).69

Breakfast (every morning)

665(79.4%)

884(81.3%).28

Snack between meals (no)585

(79.3%)

721(77.0%).27

Proportion of participants with 6 or 7 total number ofhealthy lifestyle items

212(32.9%)

281(33.5%).82

Hypertensive medication (yes)Systolic blood pressure (mm Hg)
Diastolic blood pressure (mm Hg)
Diabetic medication (yes)200(22.5%)

210(18.0%)

.01

124.9

(15.9)

124.4(15.6).47

77.1(10.1)

77.1(10.2).47

50(5.6%)

79(6.8%).29

Fasting blood glucose (mg/dL)

101.5(18.2)

101.1(17.4).70

Hemoglobin A1c (%)

5.8

(0.6)

5.9

(0.6)

.04

Fasting immunoreactive insulin

7.7

(6.3)

8.0

(5.4)

.34

C-peptide immunoreactivity

1.75(0.86)

1.71(0.77).03

Dyslipidemia medication (yes)Total cholesterol (mg/dL)

75(8.4%)

115(9.9%).27

201.3(34.3)

207.6(34.6)<.01

High-density cholesterol (mg/dL)

61.8(16.7)

61.4(16.3).58

Low-density cholesterol (mg/dL)

112.7(28.3)

118.4(30.0)<.01

Triglyceride (mg/dL)
Hyperuricemia medication (yes)108.0(85.0)

116.5(84.6)

.03

32

(3.6)

35

(3.0)

.45

Uric acid (mg/dL)

5.5

(1.3)

5.5

(1.3)

.53

Total protein (g/dL)

7.0

(0.4)

7.1

(0.4)

<.01

Albumin (g/dL)

4.2

(0.3)

4.4

(0.3)

<.01

Hemoglobin (g/dL)

14.1

(1.3)

14.3

(1.3)

<.01

High-sensitivity C-reactive protein (mg/dL)

0.14(0.47)

0.10(0.26).03

Organ damage/cardiovascular disease
Cardiovascular disease52(5.8%)

43(3.7%).02

Cerebrovascular disease20(2.2%)

22(1.9%).56

75.0(16.9)

76.6(16.2).03

eGFR (mL/min/1.73 m 2)

Abbreviations: eGFR, estimated glomerular filtration rate; N, number; SD, standard deviation.

those >60 years, and the age-adjusted prevalence of low serum zincthat evaluated serum zinc concentrations in a US population fromwas 21.1%.

A survey that examined serum zinc levels among 202

NHANES 2011-2014 reported that the mean ± SE serum zinc con-free-living Japanese women showed that mean serum zinc concen-

centrations in males and females were 84.9 ± 0.8 and 80.6 ± 0.6 μg/

21

trations were 78 ± 12 μg/dL, and the proportion of those with low
and medium serum zinc levels (<82 μg/dL) was 66.3%. 20 A survey

dL, respectively.9 Although there are variations in serum zinc con-centrations, it is possible that 20 to 40% of these people may have

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YOKOKAWA et al.

TA B L E 2

Gender-specific basic characteristics (N = 2056)

Age (years)

Men (n = 1173)

Women (n = 883)

Mean (SD) or N (%)

Mean (SD) or N (%)

Serum zinc concentration (μg/dL)

Serum zinc concentration (μg/dL)<80 (n = 545)

≥80 (n = 628)

<80 (n = 344)

≥80 (n = 539)

62.6

58.2

60.7

60.6

(12.5)(12.9)<.01(14.0)(12.5).92

Anthropometric measurements
Body mass index (kg/m2)

24.3

(3.3)

24.5

(3.2)

.28

21.7

(3.4)

22.2

(3.5)

.06

Waist circumference (cm)

85.8

(9.5)

86.7

(9.0)

.10

78.9

(9.3)

80.1

(9.9)

.09

Alcohol consumption(non–daily drinker)

285(55.1%)

366(63.2%)<.01

254(79.9%)

434(85.4%).04

Smoking behavior(nonsmoker)

434(83.6%)

469(81.4%).34

297(93.7%)

468(92.3%).45

Exercise frequency (≥2times per week)160(32.9%)

195(34.8%).5374(25.9%)

123(26.2%).92

Body mass index(18.5-24.9 kg/m2)

336(61.7%)

365(58.1%).22

230(67.1%)

380(70.5%).28

Adequate sleep duration
(yes)

402

(79.1%)

447(79.0%).95229(75.6%)

361(74.6%).79

Healthy lifestyle characteristics

Breakfast (every morning)

412(79.2%)

477(82.2%).21

253(79.6%)

407(80.3%).80

Snack between meals (no)369

(79.7%)

384(75.7%).14

216(78.5%)

337(78.6%).99

Proportion of participants
with 6 or 7 total numberof healthy lifestyle items

120(28.9%)

141(30. %1).6992(40.2%)

140(37.7%).55

Hypertensive medication
(yes)

155

(28.4%)

135(21.5%)<.0145(13.1%)

75(13.9%).73

Systolic blood pressure(mm Hg)126.5(15.2)

126.9(14.3).67

122.4(16.8)

121.6(16.5).45

Diastolic blood pressure(mm Hg)

78.5

(9.9)

79.2

(9.9)

.25

75.0

(10.2)

74.8(10.4).78

Diabetic medication (yes)44(8.1%)

63(10.0%).25

6(1.7%)

16(3.0%).26

Fasting blood glucose(mg/dL)

105.1(18.6)

105.4(19.8).80

95.6(15.9)

96.2(12.3).57

Hemoglobin A1c (%)

5.9

(0.7)

5.9

(0.7)

.20

5.7

(0.5)

5.8

(0.5)

<.01

Fasting immunoreactive
insulin

8.1

(5.5)

8.8

(5.9)

.05

7.2

(7.3)

7.1

(4.5)

.83

C-peptide
immunoreactivity

1.9

(0.9)

1.9

(0.8)

.28

1.5

(0.7)

1.5

(0.6)

.45

Dyslipidemia medication
(yes)

52

(9.5%)

59(9.4%).9323(6.7%)

56(10.4%).06

Total cholesterol (mg/dL)

195.7(33.0)

200.3(34.4).02

210.0(34.4)

216.1(33.0)<.01

High-density cholesterol(mg/dL)

56.9(15.5)

55.4(13.8).10

69.6(15.6)

68.3(16.3).24

Low-density cholesterol(mg/dL)

115.1(28.0)

119.1(30.4).02

123.2(29.7)

128.5(28.7)<.01

Triglyceride (mg/dL)

121.6(98.2)

132.8(100.1).05

86.6(51.6)

97.5(56.2)<.01

Hyperuricemia medication
(yes)

32

(5.9)

35

(5.6)

.83

0

(0.0)

0

(0.0)

6.0

(1.2)

6.2

(1.2)

.02

4.7

(1.1)

4.8

(1.1)

Uric acid (mg/dL).18(Continues)

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YOKOKAWA et al.

TA B L E 2(Continued)

Total protein (g/dL)

Men (n = 1173)

Women (n = 883)

Mean (SD) or N (%)

Mean (SD) or N (%)

Serum zinc concentration (μg/dL)

Serum zinc concentration (μg/dL)<80 (n = 545)

≥80 (n = 628)

<80 (n = 344)

≥80 (n = 539)

6.9

7.1

7.0

7.1

(0.4)

(0.4)

<.01

(0.4)

(0.3)

<.01

Albumin (g/dL)

4.2

(0.3)

4.4

(0.3)

<.01

4.2

(0.3)

4.3

(0.2)

<.01

Hemoglobin (g/dL)

14.6

(1.2)

15.1

(1.1)

<.01

13.2

(1.0)

13.5

(1.0)

<.01

High-sensitivity C-reactive
protein (mg/dL)

0.15(0.48)

0.11(0.30).13

0.12(0.44)

0.09(0.21).18

Organ damage
Cardiovascular disease

42(7.7%)

31(4.9%).05

10(2.9%)

12(2.2%).53

Cerebrovascular disease14(2.6%)

14(2.2%).70

6(1.7%)

8(1.5%).76

72.0(14.9)

75.7(16.6)<.01

79.8(18.7)

77.8(15.8).09

eGFR (mL/min/1.73 m2)

Abbreviations: eGFR, estimated glomerular filtration rate; N, number; SD, standard deviation.

serum zinc deficiency/marginal deficiency. Therefore, it is necessary

concentrations did not decrease between middle-age and elderly

to assess zinc status among free-living populations as well as subject

subjects in either gender (55-70 years: females, 13.01 ± 1.37 µmol/L,with taste or smell dysfunction.

males, 12.98 ± 1.63 µmol/L; >70 years: females, 13.18 ± 2.31 µmol/L,

Our results showed gender- and age-specific findings associatedwith serum zinc concentrations. Serum zinc concentrations were sig-male, 13.23 ± 1.70 µmol/L).23 Therefore, age-specific trends in serum
zinc concentrations are also still controversial.

nificantly lower, and the proportion of serum zinc deficiency/marginal

Differences between ages and genders may possibly be ex-

deficiency was significantly higher in men compared with women. A

plained based on normal zinc intakes. A Japanese survey re-previous study that surveyed serum zinc levels in 1009 Japanese rural

ported a positive relationship between zinc intake and serum

inhabitants showed that the proportion of subjects with serum zinc

zinc concentrations among elderly subjects (R 2 = .271). 21 The

concentrations lower than the cutoff point was significantly higher inJapanese National Health and Nutrition Survey (2017) showed

men compared with women in those >40 years, whereas no differ-that age-stratified zinc intakes were 9.1 mg/d among thoseences were observed among those <40 years.21 The Tromsø Study,

aged 30-39 years, 8.8 mg/d among those aged 40-49 years,a cross-sectional, population-based survey that evaluated the asso-

9.2 mg/d among those aged 50-59 years, 8.7 mg/d among thoseciation between the risk of malnutrition and zinc deficiency among

aged 60-69 years, and 8.7 mg/d among those aged 70-79 years

743 men and 778 women aged 65-87 years in Norway, reported thatamong men, whereas respective values were 6.4, 6.8, 7.3, 8.2, andzinc deficiency was found in 10.1% of participants, including 13.1%

8.5 mg/d, respectively, among women.15 Based on the “Dietary

7of men and 7.3 % of women. On the other hand, serum zinc con-reference intake for Japanese (2015),” established by the Japanese

centrations were significantly higher in men compared with women

government, intake of 10 mg/d zinc for men and 8 mg/d for womenin a US population (84.9 ± 0.8 and 80.6 ± 0.6 μg/dL, respectively;

is recommended. 24 However, the actual intake of zinc was shown

P < .0001). Therefore, the association between serum zinc deficiency

to be below the recommended level among middle-aged and el-

and gender is still controversial. Several possible factors are related toderly Japanese men, whereas it was sufficient among women ofzinc deficiency, including malnutrition, alcohol consumption, and zincalmost all ages. 24 The Tromsø Study reported that zinc deficiency

97,22-23

Additional studies that include thesewas found in 12.0% of men and 6.7% of women among those at low

intermediate factors are needed to determine differences in zinc defi-

supplementation status.

risk of malnutrition, whereas 31.0% of men and 12.7% of women

ciency between men and women.

had zinc deficiency among those at medium/high risk of malnutri-

Our results showed a negative association between age and serumtion.7 Our data showed that TP, Alb, and lipid profiles were signifi-

zinc levels in men, whereas no association was observed in women.

cantly lower in deficiency/marginal zinc deficiency compared to

Although these results seem paradoxical, a similar result was reported

subjects with normal zinc levels in both genders. It is possible thatin a US survey.9 The previous report showed that serum zinc concen-

the age-specific trend in serum zinc concentrations may be related

trations were significantly decreased with age in men (87.0 ± 1.6 µg/dL

to actual age-specific nutritional status, although our study couldin those aged 19-30 years vs 81.8 ± 1.8 µg/dL in those aged ≥71 years,

not estimate nutritional status, including zinc intake. Our data may

P = .02), whereas no association with age was seen in women.9 On

indicate the necessity to manage nutritional status, including zinc

the other hand, the ZENITH study, which surveyed 387 volunteers

intake, among middle-aged or elderly subjects based on officialfrom France, United Kingdom, and Italy, reported that serum zincrecommendations.

| 7

YOKOKAWA et al.

F I G U R E 2 Relationship between age
categories and serum zinc concentrations
among males (A) and females (B)(A)
Serum zinc
(μg/dl)P< 0.01 for trend

90

**
**

(n = 82)80**(n = 167)(n = 268)(n = 362)(n = 294)

70

< 40

40 to < 50

50 to < 60

60 to < 70

Age categories(years)70(B)
Serum zinc
(μg/dl)P = 0.32 for trend90(n=186)80(n=269)(n=125)(n=64)(n=239)70< 40

40 to < 50

50 to < 60

60 to < 70

70

Age categories(years)In the results, SUA was significantly higher in the normal

may be inherently more aware of their health behaviors relative togroup compared with deficiency/marginal zinc deficiency in men.

residents in rural areas. Further analyses that include data from a

Generally, serum zinc concentration is likely to be inversely cor-more diverse cohort are needed. Second, some key data on items

related with SUA, and a previous report indicated that dietary zincsuch as use of zinc supplements, eating behaviors, nutritional status,

intake is inversely associated with hyperuricemia in the Unitedclinical symptoms, serum copper concentration, and liver-relatedStates in both genders, independent of some major confounding

items were not collected. Another prospective studies including thefactors. 25 Although our finding seems to be contradicting, there

information are needed in future. Although it is necessary to discuss

is no association between serum zinc status and SUA in additional

the roles of gender hormones and gut microbiota to assess serum

logistic regression analysis adjusting lipid profiles, TP, Alb, Hb, al-zinc status in aging, it was complicated to investigate in the study. 26-

cohol consumption status, and eGFR (P = .55). Further analysis

27

focusing on the association between serum zinc status and SUA

serum zinc concentration in aging and these roles.

may be required.

Additional study is needed to discuss the association between
In conclusion, this cross-sectional study clarified a high propor-

Our study has several limitations. First, selection bias may havetion of serum zinc deficiency/marginal deficiency, and a significantly

occurred, as participants consisted of those who underwent medical

higher prevalence in men compared with women. Older age catego-checkups in a single medical institution. As such, these participants

ries showed a positive linear association with serum zinc levels only

8|

YOKOKAWA et al.

in men. The deficiency/marginal deficiency group had significantly
lower TC, LDL-C, TG, TP, Alb, Hb, and proportion of non–daily drinkers in both genders. Collectively, these findings suggest a possible
association between serum zinc levels and nutritional status andhealth behaviors, such as alcohol consumption. It may be necessary
to manage nutritional status, including zinc intake.
AC K N OW L E D G E M E N T
The authors thank all participants who underwent the voluntary
medical checkups, as well as the data collection staff at Juntendo
University.
C O N FL I C T O F I N T E R E S T
TN is a supervisor of Nobelpharma Co., Ltd (Tokyo, Japan). Other
authors do not have any conflicts of interests.
E T H I C A L A P P R OVA L
The Ethics Committee of Juntendo University reviewed and approved the research protocol using the retrospective data (No 18296), and written comprehensive informed consent was obtained
from all participants when they received health checkup.
ORCID
Hirohide Yokokawa

https://orcid.org/0000-0001-9464-9828

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How to cite this article: Yokokawa H, Fukuda H, Saita M, etal. Serum zinc concentrations and characteristics of zinc
deficiency/mild deficiency among Japanese subjects. J. Gen.
Fam. Med.. 2020;00:1–8. https://doi.org/10.1002/jgf2.377