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

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Presentation on theme: "1 Dr. Nhiên và Giáo sư Yutaka Nakaya ngày chia tay."— Presentation transcript:

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

2 22 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

3 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 4 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 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 66 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,

7 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

8 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 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.

10 10

11 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 12 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.

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

14 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 15 Thiếu selenium có phải là vấn đề sức khỏe cộng đồng ở Việt nam và các nước trên thế giới???

16 16 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.

17 17 Selenium deficiency may contribute to anemia among dialysis patients and adults with pulmonary tuberculosis 1,2. 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 2 Life Support Syst 1985;3:36-40; 3 Eur J Clin Nutr 2005;59:526-32

18 18 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

19 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

20 20  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

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

22 22  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 level Multi-elemental coverage: almost all elements Fast analysis time: few minutes/sample Wide analytical detection range: up to 9 orders

23 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

24 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

25 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

26 26 Anthropometry, iron status indicators and serum vit. A among adult Vietnamese ParameterAnemic group (n = 37) Non-anemic group (n = 86) Total (n=123) Weight (kg) 44.6  6.4 (a) 49.5  7.247.8  7.6 Height (cm) 151.5  7.1 (b) 156.1  8.1154.7  8.0 BMI (kg/m 2 ) 19.4  1.920.1  2.119.9  2.0 Hb (g/L)107.4 ± 16.6136.6 ± 10.5127.8 ± 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  0.922.06  0.92 (a) P<0.001; (b) P<0.05; (c) Geometric mean (95% CI)

27 27 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  3.114.7  3.1 Iron 135.6  90.1 (a) 222.5  122.5194.6  121.0 Copper 104.5  19.9108.0  24.4106.9  22.4 Zinc115.7  61.2114.2  30.6114.7  41.9

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

29 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 Stunting45 (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 Wasting17 (12.4%)18 (17%)35 (14.4%) * Mean ± SD; ** n (%)

30 30 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 ± 10.7107.2 ± 11.6107.8 ± 11.1 Anemia, n (%)74 (54%)61 (57.5%)135 (55.6%) WHO Category of public health significancePrevalence of anemia (%) Severe≥ 40 Moderate20.0 – 39.9 Mild5.0 – 19.9 Normal≤ 4.9

31 31 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 significancePrevalence of VAD (%) Severe≥ 20% Moderate10.0% – 20.0% Mild≥2.0% - ≤ 10.0%

32 32 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 ±18.663.9 ± 18.265.3 ± 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 Deficiency116 (87.2%)90 (86.5%)206 (86.9%) Mg (mg/L) 18.0 ± 1.818.1 ± 1.518.0 ± 1.7 Mg Deficiency72 (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 Deficiency3 (2.2%)1 (1%)4 (1.7%) * Mean ± SD; ** n (%); *** Geometric mean (95% CI)

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

34 34 Risk factors for anemia and low micronutrient levels Dependent variableIndependent variablesOdd Ratio95% CIP-value AnemiaSe deficiency2.801.63-4.800.0002 Serum retinol <1.05 µmol/L1.831.10–3.050.021 Age (per year)0.770.64-0.920.04 Gender, stuntingNS Se deficiencyAnemia2.801.63-4.800.0002 Gender, age (per year), stuntingNS Zn deficiencyMg deficiency3.091.36-7.030.007 Gender, age (per year), stuntingNS Mg deficiency Zn deficiency3.091.36-7.030.007 Age (per year)0.790.66-0.940.009 Gender, stuntingNS Serum retinol <1.05 µmol/L Anemia1.831.10–3.05<0.021 Gender, age (per year), stuntingNS NS: not significant

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

36 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

37 37 Risk factors for anemia and low micronutrient levels among primary school children Dependent variableIndependent variablesOdd Ratio95% CIP-value AnemiaSe <70 µg/L1.851.06-3.24<0.05 Serum retinol <1.05 µmol/L2.051.25–3.36<0.01 Age (per year)1.591.16-2.18<0.01 Gender, stuntingNS Se <70 µg/LAnemia1.851.06-3.24<0.05 Zn <650 µg/L, Mg <18 mg/L, Gender, age (per year) NS NS: not significant

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

39 39 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 significancePrevalence of anemia (%) Severe≥ 40 Moderate20.0 – 39.9 Mild5.0 – 19.9 Normal≤ 4.9

40 40 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/L173 (59.5%) Copper (µg/L)1005 ± 184 Cu <750 µg/L25 (8.6%)

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

42 42 Risk factors for anemia and low level of trace elements Dependent variableIndependent variablesOdd Ratio 95% CIP-value Anemia § Se <70 µg/L5.362.57–11.18<0.0001 Zn <750 µg/L1.400.71-2.76NS BMI <17.002.721.37-5.370.004 Age (per year)1.351.14-1.59<0.001 Se <70 µg/L ¶ Anemia5.362.57–11.18<0.0001 Zn <750 µg/L1.280.61-2.71NS BMI <17.002.651.25-5.610.011 Age (per year)1.130.95-1.33NS Zn <750 µg/L ¶ Anemia1.400.71-2.76NS Se <70 µg/L1.280.61-2.71NS BMI <17.000.940.53-1.68NS Age (per year)0.890.77-1.02NS § cutoffs according to WHO, 2001; ¶ cutoffs according to Sauberlich, 1999; NS: not significant

43 43 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/m 2 ) 17.1 ± 2.2 BMI**<5% percentile50 (20.7%) * Mean ± SD; ** N (%)

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

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

46 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 47 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

48 48  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)

49 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

50 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 51


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