1. Dr. Nhiên và Giáo sư Yutaka Nakaya ngày chia tay

2. Association of Selenium Deficiency to Anemia in Rural Vietnam
Biol Trace Elem Res 2006; 111: 1-9
Asia Pac J Clin Nutr 2008; 17: 48-55
J Nutr Sci Vitaminol 2008 Dec;54(6):
Nutrition 2009 Jan;25(1):6-10
By Nguyen Van Nhien
Nguyen Van Nhien MD, PhD
National Institute of Nutrition Vietnam 2 2

3. 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

4. Global Prevalence of Iron, Vitamin A and Iodine Deficiencies
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

5. 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

6. 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. 6
APJCN16(1): ; Hanoi Medical Publishing House 2003,

7. Anemia
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 7

8. Essential trace elements
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. 8

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– J Am Chem Soc 1957;79:3292– Science 1973;179: 588–90.

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

12. Selenium and Public Health
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).
1. Chin Med J 1979;92:471–6. 2. Science 1984;223:491–3. 12

13. Nguồn chính cung cấp selenium
Rich sources of selenium:
Seafood
Red meats
Kidney
Liver
Garlic
Excellent source of selenium

14. 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)

15. Thiếu selenium có phải là vấn đề sức khỏe cộng đồng ở Việt nam và các nước trên thế giới???

16. Selenium related to anemia
Low selenium levels have been associated with anemia in older adults living in USA
Eur J Clin Nutr 2009 Jan;63(1):93-9. 16

17. Selenium related to anemia
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.
2Life Support Syst 1985;3:36-40; 3Eur J Clin Nutr 2005;59:526-32 17

18. Rationale
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. 18

19. 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 19

20. Subjects and methods
Subjects: preschool children aged 1-5 yrs; primary schoolchildren 6-9 yrs adolescent girls 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.
Thai nguyen
Bavi, Hatay
Hanoi
Hanam 20

21. Data Collections Nutritional status: weight, height
Fasting blood was collected in the morning
Sera were stored at –70oC until analysis 21

22. Determination of trace elements, Hb, and Vit. A
Trace Elements: Inductively Coupled Plasma Mass Spectrometer (ICP-MS)
High sensitivity: ppt detection level
Multi-elemental coverage: almost all elements
Fast analysis time: few minutes/sample
Wide analytical detection range: up to 9 orders
Vitamin A: HPLC
Hb: Cyanmethemoglobin Method 22

23. 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/L
Magnesium <18.0 mg/L
Zinc <650 g/L for preschool children
<750 g/L for adolescent girls.
Vitamin A deficiency (IVACG 1982);
Serum retinol <0.70 mol/L 23

24. 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 24

25. Study in Vietnamese adults
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. 25 25

26. Anthropometry, iron status indicators and serum vit
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)

27. Mean serum levels of trace elements in adult Vietnamese
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
(a)P<0.001

28. Study in preschool children
Subjects were selected from 3 rural, mountainous communes in Thainguyen province, Vietnam. 28

29. 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 (%)

30. Category of public health significance Prevalence of anemia (%)
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 30

31. Category of public health significance
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% 31

32. * Mean ± SD; ** n (%); *** Geometric mean (95% CI)
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)***
(1038.1; )
(1021.9; )
(1041.4; )
Cu Deficiency
3 (2.2%)
1 (1%)
4 (1.7%)
* Mean ± SD; ** n (%); *** Geometric mean (95% CI)

33. Prevalence of multiple micronutrient deficiencies among preschool children in rural Vietnam33

34. Risk factors for anemia and low micronutrient levels
Dependent variable
Independent variables
Odd Ratio
95% CI
P-value
Anemia
Se deficiency
2.80
0.0002
Serum retinol <1.05 µmol/L
1.83
1.10–3.05
0.021
Age (per year)
0.77
0.04
Gender, stunting NS
Gender, age (per year), stunting
Zn deficiency
Mg deficiency
3.09
0.007
0.79
0.009
<0.021
NS: not significant

35. Study in primary school children
Subjects were selected from 3 primary schools in Bacninh province, Vietnam 35 35

36. 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 36

37. Independent variables
Risk factors for anemia and low micronutrient levels among primary school children
Dependent variable
Independent variables
Odd Ratio
95% CI
P-value
Anemia
Se <70 µg/L
1.85
<0.05
Serum retinol <1.05 µmol/L
2.05
1.25–3.36
<0.01
Age (per year)
1.59
Gender, stunting NS
Zn <650 µg/L, Mg <18 mg/L, Gender, age (per year)
NS: not significant

38. Study in adolescent girls
Subjects were selected from 3 schools in Hanam province, Vietnam 38 38

39. Category of public health significance Prevalence of anemia (%)
Hemoglobin concentration and prevalence of anemia among adolescent girls living in rural Vietnam
Age (years)
(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 39

40. Trace element concentrations and prevalence of low levels in serum among adolescent girls living in rural Vietnam
Age (years)
11.00 – (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%) 40

41. Prevalence of anemia and low serum trace elements by BMI category41

42. 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 NS
BMI <17.00
2.72
0.004
Age (per year)
1.35
<0.001
Se <70 µg/L ¶
Anemia
1.28
2.65
0.011
1.13
Zn <750 µg/L ¶
0.94
0.89 42
§ cutoffs according to WHO, 2001; ¶ cutoffs according to Sauberlich, 1999; NS: not significant

43. Physical characteristics of adolescent girls in rural Vietnam
Age (years)
(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 (%) 43

44. Discussion antioxidant glutathione peroxidase
Erythrocyte Hb
Selenium
Free radical
Protects hemoglobin against oxidation
via glutathione peroxidase

45. Biliverdin Carbon monoxide Heme Fe+2 Selenium Deficiency
Upregulation
Selenium Deficiency
Hepatic heme oxygenase-1
Biliverdin
Carbon monoxide
Fe+2
Heme

46. 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.

47. Conclusions 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. 47

48. Conclusions (cont) In primary school children: In Adolescent Girls:
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.

49. Future Directions for Research
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. 49 49

50. 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.

51. Thank you very much