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Dr. Nhiên và Giáo sư Yutaka Nakaya ngày chia tay

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Association of Selenium Deficiency to Anemia

in Rural Vietnam

Nguyen Van Nhien MD, PhDNational Institute of Nutrition Vietnam

Biol Trace Elem Res 2006; 111: 1-9Asia Pac J Clin Nutr 2008; 17: 48-55

J Nutr Sci Vitaminol 2008 Dec;54(6):454-459Nutrition 2009 Jan;25(1):6-10

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NỘI DUNG TRÌNH BÀY

• Điểm qua tình hình thiếu vi chất, thiếu máu ở trên thế giới và Việt Nam

• Lịch sử xuất hiện của selenium

• Vai trò sinh học của selenium

• Thiếu selenium một vấn đề sức khỏe cộng đồng quan trọng ở Việt nam!!!

• Hướng nghiên cứu trong tương lai và biện pháp phòng chống

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Micronutrient deficiencies are major public health problem in the world.

Global Prevalence of Iron, Vitamin A and Iodine Deficiencies

2 billion suffer from zinc deficiency

2 billion suffer from iron deficiency

600 million - iodine deficiency disorders

250 million children are vitamin A deficient

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Anemia is a global public health problem affecting both developing and developed countries with major consequences for human health. It occurs at all stages of the life cycle, but is more prevalent in children and pregnant women.

Worldwide prevalence of anemia 1993–2005. WHO Global Database on Anemia

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The Public Health Problem in Vietnam

Nutritional deficiencies are the leading public health problems in Vietnam:

Anemia, Vitamin A Deficiency among preschool

children, school children, pregnant women and

non-pregnant women

No available data on profile of trace element

deficiencies such as Se, Zn, Mg, and Mo in children

and adults.

APJCN16(1):152-157; Hanoi Medical Publishing House 2003,

77

Anemia is an indicator of both poor nutrition and poor health. The

consequences including:

Social and economic development.

Cognitive performance, behavior

Physical growth of children

Immune status, morbidity from infections.

Epidemiological studies have shown

Iron deficiency is a main cause of anemia

Association of vitamin A deficiency to anemia

A few studies have been done to describe the relationship of anemia

with deficiency in trace elements

Anemia

88

Trace elements (Se, Zn, Cu, Mg, and Mo) are essential nutrients

with regulatory, immunologic, and antioxidant functions

resulting from their action as essential components or cofactors

of enzymes throughout metabolism.

Essential trace elements

9

Selenium: Historical Background

• Selenium was identified as a new chemical element in

1817 (1).

• Selenium was recognized to be an essential micronutrient

in 1957, when they observed that selenium prevented liver

necrosis in vitamin E-deficient rats (2).

• Selenium was found to be a constituent of the enzyme

glutathione peroxidase in 1973 (3).

1. Ann Physik 1818;29:229–54. 2. J Am Chem Soc 1957;79:3292–3. 3. Science 1973;179: 588–90.

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Selenium and Iodine

Se is essential for the biosynthesis and

function of a small number of selenocysteine

- containing selenoproteins implicated in

thyroid hormone metabolism and gland

function.

Se-dependent glutathione peroxidases are

implicated in thyroid gland protection.

Mol Nutr Food Res. 2008 Nov;52(11):1235-46

1212

The importance of selenium to human health was recognized in 1979,

when Chinese scientists discovered that selenium supplementation

protected against Keshan disease, an endemic cardiomyopathy that

occurs primarily among children living in areas of China with selenium-

poor soils (1).

In 1984, selenium deficiency was shown to be associated with widespread

anemia among cattle grazing in selenium-poor areas in the Florida,

USA, and selenium supplementation prevented the anemia (2).

Selenium and Public Health

1. Chin Med J 1979;92:471–6. 2. Science 1984;223:491–3.

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Nguồn chính cung cấp selenium

Rich sources of selenium:

Seafood

Red meats

Kidney

Liver

GarlicExcellent source of selenium

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Nhu cầu selenium

Nhu cầu khuyến nghị (FAO/WHO - 2002): 20-50 µg/ngày

Trung quốc: nhiều vùng chỉ đạt 13.4 µg/ngày

Anh (1995): 33 µg/ngày

Mỹ: 80 µg/ngày

Việt Nam (ước tính): 20 µg/ngày

(chưa kể mất mát khi chế biến)

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Thiếu selenium có phải là vấn đề sức khỏe cộng đồng ở Việt

nam và các nước trên thế giới???

1616

Low selenium levels

have been

associated with

anemia in older

adults living in

USA

Selenium related to anemia

Eur J Clin Nutr 2009 Jan;63(1):93-9.

1717

Selenium deficiency may contribute to anemia among dialysis patients

and adults with pulmonary tuberculosis1,2.

These observations in humans are consistent with studies in animals,

which have shown that selenium deficiency is associated with

anemia.

At present, selenium deficiency should be considered a possible cause

of anemia.

Selenium related to anemia

2Life Support Syst 1985;3:36-40; 3Eur J Clin Nutr 2005;59:526-32

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• High prevalence of anemia and micronutrient 　deficiency has been reported in developing

countries, including Vietnam.

• A few studies assessed serum levels of trace

elements in children and adults. No study on

profile of serum trace elements and anemia

among these subjects in Vietnam.

• A better understanding of the interactions among

anemia, and deficiency in essential trace

elements.

Rationale

1919

Objectives

These cross-sectional studies were aimed to assess:

Hb levels in whole blood

Serum Vitamin A

Serum levels of essential elements (Se, Zn, Fe, Cu, Mg, and

Mo)

To investigate the relationship of micronutrient

deficiencies to anemia among preschool children,

primary school children, adolescent girls, and adults

living in rural Vietnam

2020

Subjects: preschool children aged

1-5 yrs; primary schoolchildren 6-9

yrs adolescent girls 11-17 yrs. Adult

from 20 to 60 yrs.

Study area: Thainguyen, Bacninh,

Hanam and Hatay provinces, rural

Vietnam.

The subjects were chosen by

systematic random sampling.

Subjects and methods

Hanoi

Thai nguyen

Bavi, Hatay

Hanam

2121

Nutritional status: weight, height

Fasting blood was collected in the

morning

Sera were stored at –70oC until

analysis

Data Collections

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Vitamin A: HPLC

Hb: Cyanmethemoglobin Method

Determination of trace elements, Hb, and Vit. A

Trace Elements: Inductively Coupled Plasma Mass Spectrometer (ICP-MS)

High sensitivity: ppt detection levelMulti-elemental coverage: almost all elementsFast analysis time: few minutes/sampleWide analytical detection range: up to 9 orders

2323

Criteria for• Undernutrition (WHO, 1995);

• Anemia (WHO, 2001); Adults

Male: Hb<130g/L; Female: Hb<120g/L Children

<5 yrs: Hb <110 g/L; 5-9 yrs: Hb <115 g/L Adolescent girls: Hb <120g/L

• Low serum levels or trace element deficiency(Sauberlich, 1999; Hotz & Brown, 2004);

Selenium <70 g/L Copper <750 g/LMagnesium <18.0 mg/LZinc <650 g/L for preschool

children<750 g/L for adolescent girls.

• Vitamin A deficiency (IVACG 1982);Serum retinol <0.70 mol/L

2424

Statistics

Data were analyzed using the SPSS version 11.0

The independent-samples T-test was used to compare levels

of trace elements in anemic and none-anemic groups.

Logistic regression analyses were used to find the

relationships between anemia, vitamin A, and levels of trace

elements.

Statistical significance indicated when P < 0.05

2525

• Anemia was found in 30.0% of

the study population.

• The subjects who had anemia

were classified as anemic group

while the others were

designated non-anemic group.

243

292

250

123

0

50

100

150

200

250

300

1-5 yrs 6-9yrs 11-17yrs

20-60yrs

Study in Vietnamese adults

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Anthropometry, iron status indicators and serum vit. A among adult Vietnamese

Parameter Anemic group

(n = 37)

Non-anemic

group (n = 86)

Total

(n=123)

Weight (kg) 44.6 6.4 (a) 49.5 7.2 47.8 7.6

Height (cm) 151.5 7.1 (b) 156.1 8.1 154.7 8.0

BMI (kg/m2) 19.4 1.9 20.1 2.1 19.9 2.0

Hb (g/L) 107.4 ± 16.6 136.6 ± 10.5 127.8 ± 18.4

SF (g/L) 27.3 (17.3, 42.5) (a,c) 60.7(49.8, 74.0) 47.7 (38.9, 58.3)

VitA(mol/L) 1.78 0.87 (a) 2.17 0.92 2.06 0.92

(a)P<0.001; (b)P<0.05; (c)Geometric mean (95% CI)

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Mean serum levels of trace elements in adult Vietnamese

(a)P<0.001

Parameter (g/dL)

Anemic group (n = 37)

Non-anemic group (n = 86)

Total (n=123)

Selenium 13.6 2.7(a) 15.2 3.1 14.7 3.1

Iron 135.6 90.1(a) 222.5 122.5 194.6 121.0

Copper 104.5 19.9 108.0 24.4 106.9 22.4

Zinc 115.7 61.2 114.2 30.6 114.7 41.9

2828

Study in preschool children

• Subjects were selected

from 3 rural,

mountainous

communes in

Thainguyen province,

Vietnam.

243

292

250

123

0

50

100

150

200

250

300

1-5 yrs 6-9 yrs 11-17yrs

20-60yrs

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Physical characteristics of preschool children in rural Vietnam

Boys

(n = 137)

Girls

(n = 106)

Total

(n = 243)

Weight for Age Z-scores*

-1.94 ± 0.72 -2.04 ± 0.68 -1.98 ± 0.70

Underweight** 65 (47.4%) 57 (53.8%) 122 (50.2%)

Height for Age Z-scores

-1.66 ± 1.13 -1.73 ± 1.20 -1.69 ± 1.16

Stunting 45 (32.8%) 43 (40.6%) 88 (36.2%)

Weight for Height Z-scores

-1.22 ± 0.79 -1.29 ± 0.77 -1.25 ± 0.78

Wasting 17 (12.4%) 18 (17%) 35 (14.4%)

* Mean ± SD; ** n (%)

3030

Hemoglobin concentration and prevalence of anemia among preschool children living in rural Vietnam

Boys

(n = 137)

Girls

(n = 106)

Total

(n = 243)

Hb (g/L) 108.2 ± 10.7 107.2 ± 11.6 107.8 ± 11.1

Anemia, n (%) 74 (54%) 61 (57.5%) 135 (55.6%)

WHO

Category of public health significance Prevalence of anemia (%)

Severe ≥ 40

Moderate 20.0 – 39.9

Mild 5.0 – 19.9

Normal ≤ 4.9

3131

Serum retinol and prevalence of vitamin A deficiency (VAD) among preschool children living in rural Vietnam

Boys

(n = 137)

Girls

(n = 106)

Total

(n = 243)

Serum retinol (µmol/L)

1.02 (0.97; 1.07) 1.02 (0.95; 1.08) 1.02 (0.98; 1.06)

VAD, n (%) 13 (9.5%) 13 (12.3%) 26 (10.7%)

WHO

Category of public health significance Prevalence of VAD (%)

Severe ≥ 20%

Moderate 10.0% – 20.0%

Mild ≥2.0% - ≤ 10.0%

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Serum levels of trace elements and their deficiencies among preschool children living in rural Vietnam

Boys

(n = 137)

Girls

(n = 106)

Total

(n = 243)

Se (µg/L) 66.4 ±18.6 63.9 ± 18.2 65.3 ± 18.4

Se deficiency** 83 (61.9%) 66 (62.9%) 149 (62.3%)

Zn (µg/L)*** 513.8 (495.4; 532.8) 514.9 (494.1; 536.5) 514.3 (500.5; 528.4)

Zn Deficiency 116 (87.2%) 90 (86.5%) 206 (86.9%)

Mg (mg/L) 18.0 ± 1.8 18.1 ± 1.5 18.0 ± 1.7

Mg Deficiency 72 (53.7%) 52 (49.5%) 124 (51.9%)

Cu (µg/L)*** 1073.2 (1038.1; 1109.5) 1058.7 (1021.9; 1096.8) 1066.8 (1041.4; 1092.9)

Cu Deficiency 3 (2.2%) 1 (1%) 4 (1.7%)

* Mean ± SD; ** n (%); *** Geometric mean (95% CI)

3333

Prevalence of multiple micronutrient deficiencies among preschool children in rural Vietnam

20.6

28.4 28.4

17.3

5.3

0

5

10

15

20

25

30

<2 2 3 4 5

Per

cent

s

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Risk factors for anemia and low micronutrient levels

Dependent variable Independent variables Odd Ratio 95% CI P-value

Anemia Se deficiency 2.80 1.63-4.80 0.0002

Serum retinol <1.05 µmol/L 1.83 1.10–3.05 0.021

Age (per year) 0.77 0.64-0.92 0.04

Gender, stunting NS

Se deficiency Anemia 2.80 1.63-4.80 0.0002

Gender, age (per year), stunting NS

Zn deficiency Mg deficiency 3.09 1.36-7.03 0.007

Gender, age (per year), stunting NS

Mg deficiency Zn deficiency 3.09 1.36-7.03 0.007

Age (per year) 0.79 0.66-0.94 0.009

Gender, stunting NS

Serum retinol <1.05 µmol/L

Anemia 1.83 1.10–3.05 <0.021

Gender, age (per year), stunting NS

NS: not significant

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243

292

250

123

0

50

100

150

200

250

300

1-5 yrs 6-9 yrs 11-17yrs

20-60yrs

Study in primary school children

• Subjects were

selected from 3

primary schools in

Bacninh province,

Vietnam

3636

Trace element concentrations and prevalence of low levels in serum among primary school children living in rural Vietnam

Age (years) 6.00 – 9.00

(n = 292)

Selenium (µg/L) 61.0 ± 13.6

Se <70 µg/L, n (%) 220 (75.6%)

Zinc (µg/L) 475.7 (464.1; 487.7)

Zn <650 µg/L, n (%) 266 (91.4%)

Magnesium (mg/L) 2.54 ± 0.28

Copper (µg/L) 1005 ± 184

Molybdenum (µg/L) 0.33 ± 0.15

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Risk factors for anemia and low micronutrient levelsamong primary school children

Dependent variable Independent variables Odd Ratio 95% CI P-value

Anemia Se <70 µg/L 1.85 1.06-3.24 <0.05

Serum retinol <1.05 µmol/L 2.05 1.25–3.36 <0.01

Age (per year) 1.59 1.16-2.18 <0.01

Gender, stunting NS

Se <70 µg/L Anemia 1.85 1.06-3.24 <0.05

Zn <650 µg/L, Mg <18 mg/L, Gender, age (per year)

NS

NS: not significant

3838

• Subjects were

selected from 3

schools in Hanam

province, Vietnam

243

292

250

123

0

50

100

150

200

250

300

1-5 yrs 6-9 yrs 11-17yrs

20-60yrs

Study in adolescent girls

3939

Hemoglobin concentration and prevalence of anemia among adolescent girls living in rural Vietnam

Age (years) 11.00-17.99

(n = 245)

Hb (g/L) 126.6 ± 7.8

Anemia, n (%) 50 (20.4%)

WHO, 2001

Category of public health significance Prevalence of anemia (%)

Severe ≥ 40

Moderate 20.0 – 39.9

Mild 5.0 – 19.9

Normal ≤ 4.9

4040

Trace element concentrations and prevalence of low levels in serum among adolescent girls living in rural Vietnam

Age (years) 11.00 – 17.99 (n = 245)

Selenium (µg/L) 107 ± 34

Se <70 µg/L, n (%) 39 (15.9%)

Zinc (µg/L) 860 ± 164

Zn <750 µg/L, n (%) 65 (26.5%)

Magnesium (mg/L) 25.4 ± 2.8

Mg <18 mg/L 173 (59.5%)

Copper (µg/L) 1005 ± 184

Cu <750 µg/L 25 (8.6%)

4141

Prevalence of anemia and low serum trace elements by BMI category

22.0

25.2

12.39.6

26.327.6

0

5

10

15

20

25

30

35

40

Anemia Se <70 ug/L Zn <750 ug/L

%

BMI<17

BMI>=17

P=0.003

P=0.009

4242

Risk factors for anemia and low level of trace elements

Dependent variable Independent variables Odd Ratio

95% CI P-value

Anemia § Se <70 µg/L 5.36 2.57–11.18 <0.0001

Zn <750 µg/L 1.40 0.71-2.76 NS

BMI <17.00 2.72 1.37-5.37 0.004

Age (per year) 1.35 1.14-1.59 <0.001

Se <70 µg/L ¶ Anemia 5.36 2.57–11.18 <0.0001

Zn <750 µg/L 1.28 0.61-2.71 NS

BMI <17.00 2.65 1.25-5.61 0.011

Age (per year) 1.13 0.95-1.33 NS

Zn <750 µg/L ¶ Anemia 1.40 0.71-2.76 NS

Se <70 µg/L 1.28 0.61-2.71 NS

BMI <17.00 0.94 0.53-1.68 NS

Age (per year) 0.89 0.77-1.02 NS§ cutoffs according to WHO, 2001; ¶ cutoffs according to Sauberlich, 1999; NS: not significant

4343

Physical characteristics of adolescent girls in rural Vietnam

Age (years) 11.00 - 17.99

(n=245)

Height* (cm) 147.7 ± 9.1

Weight (kg) 37.7 ± 7.8

BMI (kg/m2) 17.1 ± 2.2

BMI**<5% percentile 50 (20.7%)

* Mean ± SD; ** N (%)

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Free radical

glutathione peroxidase

antioxidant

Erythrocyte

Hb

Selenium

Protects hemoglobin against oxidation

via glutathione peroxidase

Discussion

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Selenium Deficiency

HemeBiliverdinCarbon monoxideFe+2

Hepatic heme oxygenase-1

Upregulation

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Selenium deficiency leading to anemia

• A mechanism by which selenium deficiency could potentially

contribute to anemia is through modulation of inflammation. Low

serum Se concentrations among disabled older women living in the

USA were predictive of subsequent increase in interleukin (IL)-6.

• Thus, Se could potentially play a role in the anemia of chronic

inflammation through its relationship with the upregulation of IL-6.

• In turn, IL-6 has been implicated in the upregulation of hepcidin, the

iron regulatory hormone that blocks iron absorption in the gut and

iron release from macrophages and the liver.

4747

In Adults:

The incidence of anemia was 30% and lower serum selenium

levels were found in anemic compared to non-anemic groups.

In Preschool Children:

Prevalence of anemia: 55.6%; Vitamin A deficiency: 10.7%

Se deficiency was 65.3%, Zn deficiency was 86.9%, Mg deficiency was

51.9% and Cu Deficiency was 1.7%.

The first data showed a strong association of selenium deficiency

with anemia in children.

Conclusions

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In primary school children:

Prevalence of anemia and VAD was 45.2%, and 11.3%, respectively.

Prevalence of zinc, selenium, and magnesium deficiency in the

children was 91.4%, 75.6%, 59.5%, respectively.

The results showed an association of low serum Se with anemia.

In Adolescent Girls:

Prevalence of anemia was 20.4%; low serum Se was 15.9% and low

serum Zn 26.5%.

The results showed a strong association of low serum Se with

anemia.

Conclusions (cont)

4949

Se deficiency is associated with anemia among preschool children, school

children, adolescent girls, and adults living in rural Vietnam.

Important public health question? Does Se deficiency contribute to anemia

in other populations at high risk for anemia, such as pregnant women? non-

pregnant women? It is not known whether improving dietary Se intake will

increase Hb levels among populations with Se deficiency?

Given the present findings, it is urgent that well-designed clinical control

trials will provide the strongest evidence for the role of Se in anemia among

human populations.

Future Directions for Research

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Future Directions for Research

• Indications that a suboptimal selenium status may have much wider significance in influencing disease susceptibility must be pursued.

• Studies must cover both the impact of selenium deficiency on protection against oxidative damage during tissue trauma and its genetic implication for viral virulence.

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