Dr. Nhiên và Giáo sư Yutaka Nakaya ngày chia tay

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

2. Association of Selenium Deficiency to Anemia in Rural Vietnam Nguyen Van Nhien MD, PhD National Institute of Nutrition 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):454-459 Nutrition 2009 Jan;25(1):6-10 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 • 2 billion suffer from zinc deficiency • 600 million - iodine deficiency disorders • 250 million children are vitamin A deficient • 2 billion suffer from iron deficiency Micronutrient deficiencies are major public health problem in the world.

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):152-157; 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;29:229–54. 2. J Am Chem Soc 1957;79:3292–3. 3. Science 1973;179: 588–90.

11. 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

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 micronutrientdeficiency 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 Thai nguyen Bavi, Hatay Hanoi • 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. 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) • Vitamin A: HPLC • Hb: Cyanmethemoglobin Method 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 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 comparelevels 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. 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. Study in Vietnamese adults 25

26. Anthropometry, iron status indicators and serum vit. A among adult Vietnamese (a)P<0.001; (b)P<0.05; (c)Geometric mean (95% CI)

27. Mean serum levels of trace elements in adult Vietnamese (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 * Mean ± SD; ** n (%)

30. Hemoglobin concentration and prevalence of anemia among preschool children living in rural Vietnam 30

31. Serum retinol and prevalence of vitamin A deficiency (VAD) among preschool children living in rural Vietnam 31

32. Serum levels of trace elements and their deficiencies among preschool children living in rural Vietnam * Mean ± SD; ** n (%); *** Geometric mean (95% CI)

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

34. Risk factors for anemia and low micronutrient levels NS: not significant

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

36. Trace element concentrations and prevalence of low levels in serum among primary school children living in rural Vietnam 36

37. Risk factors for anemia and low micronutrient levelsamong primary school children NS: not significant

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

39. Hemoglobin concentration and prevalence of anemia among adolescent girls living in rural Vietnam 39

40. Trace element concentrations and prevalence of low levels in serum among adolescent girls living in rural Vietnam 40

41. Prevalence of anemia and low serum trace elements by BMI category P=0.003 P=0.009 41

42. Risk factors for anemia and low level of trace elements 42 §cutoffs according to WHO, 2001; ¶cutoffs according to Sauberlich, 1999; NS: not significant

43. Physical characteristics of adolescent girls in rural Vietnam 43 * Mean ± SD; ** N (%)

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

45. 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: 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. 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 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.