C Ramachandran Memorial Lecture 2012

Transcription

1 C Ramachandran Memorial Lecture 2012 Changing scenario of micronutrient deficiencies B Sesikeran MD., FAMS.,FIMSA.,FAPAS Former Director, National Institute Nutrition, Hyderabad

2 In the study of the science of nutrition, lies the greatest hope for the future of medicine - Sir. Robert McCarrison Founder Director of NIN

3 This is where it all began in 1918

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5 Earliest documented evidence of research on Micronutrients in India Beri-Beri Enquiry at Coonoor in south India Research not only on Beri-Beri, but also on a host of other dietary deficiencies and goitre. All these experiments were conducted on experimental animals pigs, monkeys and rats (McCarrison, 1921). The pigeons served as the experimental models for his studies on Beri-Beri produced by feeding polished rice

6 The defective diets used in these experiments and in subsequent studies were a combination of natural diets, in particular those resembling the ones consumed by the communities in India. They were not artificial laboratory diets /mixtures of purified ingredients. He was the first to use this method of approach extensively in nutrition research (Aykroyd, 1969).

7 1935 Chemical analysis of over 200 foods for proximate principles (energy, carbohydrate, protein, fat and mineral content) was completed in 2 years. Simultaneously, vitamin contents of these foods were investigated. newer or improved methods of analysis were introduced especially for estimation of niacin, carotene and some B-vitamins.

8 A small clinical unit for the study of deficiency diseases was established in Stanley Hospital with Dr. C Gopalan as the clinical assistant to look into diarrhoea, a nutritional disorder. An interesting observation from this clinical unit was the description of a clinical condition called 'burning feet syndrome', which was described as being due to B-vitamin deficiency, particularly, pantothenic acid; and its successful treatment with vitamin B (pantothenic acid) (Gopalan, 1946; 1949).

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10 Vitamin A deficiency to develop strategies for control and prevention of nutritional blindness. In those days, keratomalacia was one of the commonest diseases seen in ophthalmic hospitals Incorporation of vitamin A or beta-carotene rich foods in daily diets. After some preliminary animal and clinical trials (Srikantia and Reddy, 1970), the effect of oral administration of a large dose of vitamin A on serum vitamin A levels, a field trial involving 2500 children was launched. In this study, 300,000 IU vitamin A was administered orally once a year to the children and the prevalence of vitamin A deficiency and nutritional blindness were monitored over a period of five years. NRL have recommended administration of 200,000 IU each at six-monthly intervals

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12 In 1968 the Nutrition Society of India (NSI), set up a study group on Nutritional Anaemias under Dr. C. Gopalan This study group, on the basis of various studies carried out in India recommended a programme of iron folate supplementation for pregnant women and preschool children as a prophylaxis measure (NSI, 1968). In pursuance of this recommendation of NSI task force, the Government soon introduced the National Nutritional Anaemia Prophylaxis Programme targeting pregnant women and young children in 1970.

13 Through field studies, iron absorption from Indian diets based on different cereals and millets was determined among men and women. During this period, the institute also developed an in vivo method for predicting the iron bioavailability from foods and diets, which correlated highly with in vivo extrinsic tagging method (Narasinga Rao and Prabhavati, 1978). After a series of studies on the stability and bioavailability of iron in common salt fortified with iron employing different iron compounds and wide range of stabilizing agents, a successful process for fortification of salt with iron was developed (Narasinga Rao and Sarathy, 1975; Narasinga Rao et al., 1978).

14 During early part of 1980s, many studies were conducted on micronutrient deficiencies. Poor vitamin A status of pregnant women was recognized and supplementation of such women with 6000 μg of vitamin A daily for 12 weeks improved their serum vitamin A levels. Similarly, vitamin A supplementation to pregnant and lactating women also resulted in higher levels of haemoglobin as well as serum vitamin A levels in both the groups (Panth et al., 1990 ; NIN, 1990). During this period, NIN's research also focussed on development of a technology for fortification of salt with both iodine and iron (double fortified salt (DFS)) to combat both iodine deficiency disorders (IDD) and iron deficiency anaemia (IDA).

15 Prevalence of micronutrient deficiencies The global prevalence - 2 billion Mostly in the developing countries

16 Median Intake of Nutrients (as % RDA) Among 4-6 year children : By gender Percent of RDA

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18 Average Intake of Nutrients (per CU/day) as % of RDI by Period of Survey (Contd.) Percent

19 IRON deficiency

20 Prevalence (%) of Anaemia by Age, Gender & Physiological Groups Mean ±SE yr B+G Yr Girls Yr. Girls Preg. W Lact. W NPNL. W Men > 6 months < 6 months Normal Mild Moderate Severe

21 Iron (mg/1000 K cals) IRON DENSITY TO MEET RDA required iron density P r e gna nt se de nt a r y La c t a t i ng wome n C hi l dr e n: 1-3 y r s Physiological groups available iron density Computed from NNMB data, rural survey, 2001

22 Folic acid (mcg/1000 K cals) FOLIC ACID DENSITY TO MEET RDA P r e gna nt se de nt a r y La c t a t i ng wome n C hi l dr e n: 1-3 y r s required density available density Physiological groups Computed from NNMB data, rural survey, 2001

23 Anemia among Children Age 6-35 Mo Percent Any anemia Moderate anemia severe anemia NFHS-2 NFHS

24 Iodine deficiency Disorders

25 Prevalence (%) of IDD among 6 11 Year Children Maharashtra 12.2 Madhya Pradesh 4.3 Orissa 0.1 West Bengal 9.0 Karnataka 1.9 Andhra Pradesh 3.8 Pooled: 3.9 < 5 % Kerala 0.6 Tamil Nadu 0 > 5 % Source: MND-NNMB, Tech Rep 22, 2003

26 PREVALENCE (%) OF IDD AMONG CHILDREN ( 12 years old)

27 Percent of Households consuming salt having adequate Amount ( 15 ppm) of Iodine * By spot test

28 Vitamin A Deficiency 28

29 Prevalence (%) of Bitot spots among 1 - <5 year children Maharashtra 1.3 Madhya Pradesh 1.4 Orissa 0.3 West Bengal 0.6 Karnataka 0.7 Kerala 0 Tamil Nadu 0.5 Andhra Pradesh 1.2 Pooled: 0.7% < 0.5 % 0.5 % Boys: 0.9% Girls 0.6%

30 Prevalence (%) of Bitot Spots among 1 - <5 yrs. Children * WHO cut-off level (0.5%) of Public Health significance

31 Distribution (%) of 1-5 Yr. Children According to Median Dietary intake of Vitamin A (as % RDA), Prevalence of Bitot Spots, Sub-clinical Vit. A Deficiency (Blood Vit. A levels < 20 g/dl) and Extent of Coverage for Suppl. of Massive Dose Vit. A By States STATES Dietary Intake of Vitamin A < 50% of RDA Prevalen ce of Bitot Spots (%) Blood Vitamin A < 20 g/dl Receipt of Massive Dose Vitamin A 1 or 2 Doses No. of Doses One Two Kerala Tamil Nadu Karnataka AP Maharashtra MP Orissa West Bengal Pooled Source: NNMB, Tech Rep 23, 2005

32 GROUP MAN WOMAN INFANTS CHILDREN BOYS GIRLS BOYS GIRLS BOYS GIRLS CATEGORY Sedentary Moderate Retinol (µg/day) Β Carotene (µg/day) Revised Old Revised Old Heavy Sedentary Moderate Heavy Pregnant Lact. <6 mths Lact mths 0 6 mths mths yrs 4-6 yrs yrs yrs yrs yrs yrs yrs yrs

33 Zinc Deficiency

34 Zinc Status in Pregnancy Gestational age Number Zinc µg/dl Non pregnant ± < 12 weeks ± weeks ± weeks ± weeks ± >37 weeks ± Term ± Cord blood ± Gradual decrease Yasodhara et al, Nutr Research, 1991

35 Zinc Status in Maternal & Cord Blood at Term Maternal blood S level <70 /µgm Cord blood S level Radhakrishna (n=495), ± % ±24.3 Adequate Bahl L, (n=159) 1994, IJP 69.2 ± ± 14 Adequate Rathi SS et al 1999, IJP (n=40) 69.0 ± % 72.77± 5.14

36 Early post natal life source of Zinc 1. Breast milk and 2. Liver stores acquired during IU life Breast milk zinc levels decrease progressively Age Krebs et al Rajalaxmi NIN, 1991 Hemalatha NIN, month months months months >12 months Breast milk Zn levels mg/l

37 Zinc Status of Infants from Birth to 9 Months (µg/dl) Full term n=118 Preterm n=68 Formula fed n=26 Cord blood 118.3± ± ± mths 76.9 ± ± ±5.52 6mths 74.2 ± ± ±3.0 9 mths 83.8 ± ± ±7.43 Hemalata et al, 1997, J Trop ped.

38 Vegetarians diets and Zn The bioavailability of zinc from vegetarian diets is lower than from non-vegetarian diets. Meat and sea food is high in bioavailable zinc Phytates inhibit zinc absorption Regulation did not permit Zn fortification in India

39 Vitamin D deficiency 39

40 Cut off point Prevalence % Delhi, Goswami,2001 < 20 ng/ml >90% Javaid, Pregnancy. Lancet,2006 Pregnancy, NIN study, 2008 Cord blood, NIN, 2008 Alok sachan et al pregnancy Seema Puri et al Adolescent girls Harinarayan et al Tirupati, children < 20 ng/ml 84% < 20 ng/ml 87.8% < 20 ng/ml 91% < 10 ng/ml 42.5% < 20 ng/ml 90.8% < 20 ng/ml 75% 40

41 International Recommendations AAP recommends 400 iu per day in infants and children. FAO/WHO recommendations it is still 200 iu per day for all except elderly where it is 400 iu AAP recommendations aims at maintaining the vit D levels above 30ng/ml (20 ng for bone and 30 ng for other functions) Old recommendation of around 20 ng/ml where 200 iu per day is sufficient. In infants 400 iu may be good for maintaining the level above 30ng/ml the functional significance is not known. Out RDA mentions only 400 iu for all age in situations where sun exposure is inadequate. Supplemented vitamin D is fat soluble and may not reach all tissues. Sunlight generated vitamin D is water soluble.

42 B12 Deficiency 42

43 Prevalence of B12 Deficiency Cobalamin def <150pmol/L Holo TC def <35 pmol/l Hyper-hcy >15µ mol/l Elevated s. MMA >0.26 µ mol/l Yajnik n=204 AJCN % 73% 77% 73% Nepal Pregnancy EJCN, % 68% 61% Is it ok to give folic acid supplements to a B12 deficient during pregnancy 43

44 B12 Deficiency May Be More Widespread Than Thought By Judy McBride August 2, 2000 Nearly two-fifths of the U.S. population may be flirting with marginal vitamin B12 status if the population of Framingham, Mass., is any indication. A careful look at 3,000 men and women in the ongoing Framingham Offspring Study found 39 percent with plasma B12 levels in the low normal range--below 258 picomoles per liter. Nearly 9 percent of the study population fell below the current deficiency level USDA web page

45 Commonly used drugs which may interfere with B12 Absorption Proton pump inhibitors eg Omeprazole/ Lanzoprazole H2 receptor antagonists eg Ranitidine Oral anti diabetic drug metformin Source: office of dietary supplements NIH 2011

46 MAN WOMAN INFANTS CHILDREN BOYS GIRLS BOYS GIRLS BOYS GIRLS GROUP Category Vit. B12 (µg/day) Revised Old Sedentary Moderate 1 1 Heavy Sedentary Moderate 1 1 Heavy Pregnant Lact. <6 mths Lact mths 0 6 mths 6 12 mths 1-3 yrs 4-6 yrs 7-9 yrs yrs yrs yrs yrs yrs yrs

47 Fetal programming and micronutrients Micronutrients Influence metabolism Synthesis,storage secretion & function of insulin Eg., Fe, Cu, Zn, Mg, V, Vit C, A, E etc, Deficiency? Relevance to India HIDDEN HUNGER - Widely prevalent - Common in pregnant & lactating women - LBW 13 to 30%, despite supplementations. Foetal metabolic Programming

48 The Hypothesis Maternal and peri / postnatal micronutrinet restriction alters the body composition (adiposity, muscle and bone ) of the offspring, macronutrient metabolism and predisposes them to obesity, IR and associated diseases in their later life.

49 Summary of findings on trace element restriction Chronic trace element restriction (except Zn) no effects in WNIN female rats. Trace element restriction modulated body composition, adipose / muscle development / function & insulin secretion (basal & Glc stim) in offspring. Increased body fat %, central adiposity, altered expression of adipokines ( altered adipose function? ) Altered expression of genes of myogenisis, carbohydrate and lipid metabolism. MgR effects seen early, persisted late in life & mostly irreversible by rehabilitation. ZnR effects seen early, corrected by rehabilitation. CrR effects seen late, persisted long and corrected by rehabilitation variably. MnR transient effects, BUT enhanced the effects of high fat feeding, induced IR and impaired glucose tolerance. M Raghunath et al..

50 Nutrients affect gene expression mostly by epigenetic mechanism (s) such as DNA methylation, histone acetylation etc Folate, Vit B2, B6 & B12 regulate one-carbon metabolism (eg. methylation) I Imbalance of this metabolism elevates levels of s- adenosyl Hcy & Hcy, independent risk factors for IR and CVDs Folate & B12 def widespread in Indians (vegetarianism?), specially in preg & lact mothers. Maternal B12 def associated with adiposity & IR in offspring.

51 Conclusions from animal studies Chronic maternal dietary micronutrient restriction, regardless of the micronutrient being restricted, resulted in significant, mostly irreversible changes in the body composition [ increased fat ( central adiposity ) and decreased LBM and FFM % ( muscle mass?) ] and the function of the muscle and adipose tissues. Affected the metabolism of carbohydrates and lipids in the offspring and the capacity of the animal to secrete insulin ( basal and glucose stimulated ).The changes observed are consistent with their predisposition to diabetes. Interestingly, folate and / or vit B 12 deficiency altered the body composition of the mothers in addition to the effects on the offspring as mentioned above.

52 Major causes of micronutrient deficiencies in India Inadequate intake of staple with no nutritious food Poor bioavailability of minerals and vitamins Frequent intestinal parasitic infestation. Commonly consumed foods and beverages are high in inhibitors and low in enhancers of micronutrient absorption. Significant negative trend in the grain iron and zinc concentrations in the wheat cultivars.

53 Major causes of micronutrient deficiencies in India. The primitive cultivars of wheat and rice appear to have favorable nutritional characteristics compared to the currently used high yielding varieties. Reduced dietary diversity and increasing consumption of refined and processed foods

54 Countering Micronutrient Deficiencies Strategies Supplementation programs Targeted / universal, linked with immunization programs Fortification Targeted / Universal

55 Management through community based programs Reduction in LBW prevalence by Improving Maternal nutrition Wt. gain in pregnancy 0.5kg/wk in 2 nd - 3 rd trimesters Pre-pregnancy nutritional status Adolescent Improving IYCF practices Supplementary nutrition programs Food fortification 55

56 Weekly multimicronutrient supplementation programs are cost effective options in urban areas with populations with low risk of energy deficiency and high risk of micronutrient deficiencies. Even in those countries where food fortification works such as Peru and many other countries fortification alone does not satisfy the physiological needs of small children, pregnant women and most vulnerable groups Aaron Lechtig et al. F & N bulletin, Dec 2006

57 Thank you 57