Effect of micronutrient supplement on health and nutritional status of schoolchildren: biochemical status

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oniochishnDande Sreeramulu, Ph.D.b, Palla Suryanarayana, Ph.D.b, Punjal Ravinder, Ph.D.a,VAbKeyInphcar2006) S089doiVeena Shatrugna, M.D.c, Prattipati Ajey Kumar, M.Sc.c, Manchala Raghunath, Ph.D.b,araganti Vikas Rao, M.Sc.a, Nagalla Balakrishna, Ph.D.d, Putcha Uday Kumar, M.D.e, andNamala Raghuramulu, Ph.D.ba Division of Biophysics, National Institute of Nutrition (Indian Council of Medical Research), Hyderabad, Indiab Division of Endocrinology and Metabolism, National Institute of Nutrition (Indian Council of Medical Research), Hyderabad, Indiac Division of Maternal and Child Health, National Institute of Nutrition (Indian Council of Medical Research), Hyderabad, Indiad Division of Field Studies, National Institute of Nutrition (Indian Council of Medical Research), Hyderabad, Indiae Division of Pathology, National Institute of Nutrition (Indian Council of Medical Research), Hyderabad, IndiaManuscript received April 6, 2004; accepted July 23, 2005.stract Objective: We assessed the effect of a daily intake of a micronutrient-fortified beverage for 14 moon indicators of biochemical status of important micronutrients in schoolchildren.Methods: A double-blind, placebo-controlled, matched-pair, cluster, randomization study design wasused. Biochemical indicators of micronutrient status were evaluated at baseline and at the end of 14mo on a subsample in nine matched pairs. Prevalence (percentage) of subclinical deficiency, mean,and mean increments of each indicator were compared between supplemented and placebo groups.Results: Extent of inadequacy at baseline was more or less 100% for folic acid, 65% for vitaminsB2 and B6, and 55% for vitamins C and A. Prevalence of anemia among subjects was 55%, withinadequacy of vitamin B12 being 40% and that of vitamin D being 30%. No subject had inadequacyof iodine based on urinary iodine. Supplementation of a micronutrient-enriched beverage for 14 mosignificantly improved the status of many of the nutrients. The effect was significant with respect tovitamins A, B2, and B12, folic acid, vitamin D, parathyroid hormone, and thyroid-stimulatinghormone in children who received the supplement compared with those who received only placebo.Hemoglobin status improved only in children who had anemia in the supplemented group.Conclusions: Prevalence of multiple subclinical micronutrient deficiencies are high in middle-income Indian school children. Daily consumption of a micronutrient-enriched beverage hadpositive effects that were confined to those nutrients that were inadequate at baseline. 2006Elsevier Inc. All rights reserved.words: Micronutrients; Biochemical status; Nutritional supplementation; Children; Vitamins; Minerals; SubclinicaldeficiencytroductionProtein, energy, and micronutrient deficiencies affectysical work capacity, body fitness, and mental function[13]. In particular, deficiency of micronutrients such asiron, vitamin A, zinc, iodine, and B-complex vitamins havebeen shown to affect growth, maximal work capacity [3],mental function [2,3], visual acuity [4], and psychomotorfunction [5]. Supplementation of malnourished childrenwith iron and B-complex vitamins has been reported toimprove these functions [46]. Supplementation with min-This study was supported by M/S GlaxoSmithKline Consumer Health-e, Ltd., India.Effect of micronutrient supplementschoolchildren: bBattiprolu Sivakumar, Ph.D.a,*, KrNutrition 22 (eratal* Corresponding author. Tel.: 91-40-2701-8083.E-mail address: dirnin_hyd@yahoo.co.in (B. Sivakumar).9-9007/06/$ see front matter 2006 Elsevier Inc. All rights reserved.:10.1016/j.nut.2005.07.012health and nutritional status ofemical statusapillai Madhavan Nair, Ph.D.a,15S25www.elsevier.com/locate/nutls and vitamins has been associated with improved men-function [7] and growth and development of children[8supenthelatoftheinshodredesuccrogrooumapatatMistcriproarananschwamuninmeferurihoB6aftsammaelsvit[22CobadiouriplaspeserB6lysmeClinpabaindtioStabavasupevfinbecomeysiefftiaUSReBainabademedrefolwechstawasuptioS16 B. Sivakumar et al. / Nutrition 22 (2006) S15S2511]. It has been reported that the benefit of micronutrientplementation is optimal only when multiple micronutri-ts are provided [10,1214] and the effect is pronounced ifre is a basal micronutrient deficiency [1517].During the past 25 y, a large database has been accumu-ed on the diet and nutritional status of the rural populationdifferent states of India [18]. These surveys indicate thatdiets of the rural population are inadequate and deficientmost nutrients. However, there have been no studieswing the effect of micronutrient supplementation in chil-n with adequate dietary intake and no apparent clinicalficiency of macronutrients. It is worthwhile to examineh a situation because inadequate concentrations of mi-nutrients in the body may be responsible for suboptimalwth and development. To test this hypothesis, we carriedt a double-blind, placebo-controlled, cluster, randomized,tched-pair study in residential schoolchildren and com-red their micronutrient status before and after supplemen-ion.aterials and methodsThe details of the study design, composition, and admin-ration of the micronutrient-enriched beverage and othertical issues related to the methodology of the study arevided in a separate report [19]. Briefly, we have adopteddouble-blind, placebo-controlled, matched-pair, cluster,domization design. The children were 6 to 18 y of aged in grades 1 to 10 from a middle-income residentialool near Hyderabad, India. Effect on biochemical statuss assessed in a randomly selected subsample of a mini-m of 4 to a maximum of 19 from each pair. There weree matched pairs available for biochemical status assess-nt at the end of 14 mo of supplementation.Various biochemical parameters such as hemoglobin,ritin, calcium, phosphorus, parathyroid hormone (PTH),nary iodine, triiodothyronine (T3), thyroid-stimulatingrmone (TSH), albumin, zinc, vitamins A, C, D, B1, B2,, and B12, and folic acid were measured at baseline ander 14 mo.Blood samples after an overnight fast or random urineples were used for estimation. Hemoglobin was esti-ted by the cyanmethemoglobin method [20]; plasma lev-of ferritin by enzyme-linked immunosorbent assay [21];amin A by high-performance liquid chromatography]; folic acid, vitamin B12 and PTH (Diagnostic Productsrporation, Los Angeles, CA, USA), and T3 (BRIT, Mum-i, India) by radioimmunoassay kits; TSH by immunora-metric assay (BRIT, Mumbai, India); vitamin C [23],nary iodine [24], and phosphorus by colorimetry [25];sma calcium [26] and zinc [27] by atomic absorptionctrometry; vitamin D by protein binding assay [28];um albumin by dye binding [29]; vitamins B1, B2, andby enzyme activation coefficient assays in erythrocyteate [30]; and urinary riboflavin (B2) concentration was smasured fluorometrically [31]. Because analysis of vitamincould not be performed immediately, the sample at base-e was smaller but was more than adequate for all otherrameters. For vitamin B6 the number was smaller atseline due to some technical problems.For convenience in comparison, different biochemicalicators were broadly categorized according to their func-nal association with an important nutrient:1. Measurements related to hemopoiesis (hemoglobin,ferritin, vitamin C, folic acid, vitamin B12, and vita-min A)2. Measurements related to bone health (calcium, phos-phorus, vitamin D, PTH, zinc, and albumin)3. Measurements related to iodine status (T3, TSH, andurinary iodine)4. Measurements related to status of psychomotor vita-mins (vitamins B1, B2, and B6)tistical analysisThe percentage of inadequacy of micronutrient status atseline in these schoolchildren was computed from cutofflues derived from the literature [3236]. The effect ofplementation on indicators of micronutrient status wasaluated in cohort samples from the differences betweenal and baseline values. Whenever baseline differencestween groups differed (vitamin D), these differences wererrected by a regression model before testing the finalans between the supplement and placebo groups. Anal-s was also done to test whether the supplement had anyect in improving hemoglobin in children who were ini-lly anemic by t test. SPSS 11.5 (SPSS, Inc., Chicago, IL,A) was used for computation and statistical analysis.sultselineSubclinical deficiency or the proportion of children withdequate micronutrient status is presented in Table 1. Atseline, there were no significant differences in subclinicalficiency in any biochemical indicator between the supple-nted and placebo groups; except for vitamin D. All chil-n in both groups had inadequate red blood cell (RBC)ate status. More than 50% of children had anemia andre deficient in vitamin C at the beginning. About 40% ofildren had vitamin A and B12 inadequacies at baseline.The proportion of children who had poor calcium and PTHtus at baseline was low (7%) except for vitamin D, whichs high and values were significantly different between theplement (30.3%) and placebo (21.6%) groups. The propor-n with inadequacy of plasma zinc (30 mol/L) was veryall and those with inadequate vitamin B2 and B6 werewiwedefi plaTabMicRBVitVitVitHemVitVitVitVitCalPTHZinPhoT3TSHUriAgluRBcoe*Fig and RBsup nd of 1fromS17B. Sivakumar et al. / Nutrition 22 (2006) S15S25despread because more than 65% of children in both groupsre deficient at the start of the study. However, the subclinicalciency of B1 was lower (12%).le 1ronutrient status of children at baselineMicronutrient %InadequatePooled Supplement PlaceboC folate (550 nmol/L) 99.0 98.0 100.0amin B6 (1.80 AAT-AC) 66.9 65.2 68.6amin B2 (1.40 GR-AC) 66.4 66.0 65.9amin C (30 mol/L) 59.6 57.1 62.5oglobin (120 g/L) 55.7 54.8 56.6amin A (0.7 mol/L) 43.9 54.7 33.1amin B12 (150 pmol/L) 43.8 39.3 48.4amin D (25 nmol/L) 25.9 30.3* 21.6amin B1 (1.25 TK-AC) 11.7 12.2 11.3cium (2.2 mmol/L) 6.1 5.8 6.4(12 ng/L) 2.6 1.4 3.8c (10.7 mol/L) 0.7 1.3 0sphorus (0.87 mmol/L) 0 0 0(1.08 nmol/L) 2.6 1.4 3.7(0.17 mlU/L) 0.3 0.7 0nary Iodine (20 g/L) 0 0 0AT-AC, aspartate aminotransferase activation coefficient; GR-AC,tathione reductase activation coefficient; PTH, parathyroid hormone;C, red blood cell; T3, triiodothyronine; TK-AC, transketolase activationfficient; TSH, thyroid-stimulating hormoneP 0.01 by Wilcoxons sign-rank test.. 1. Initial and final levels of hemoglobin, plasma ferritin, vitamin B12,plement (white bars) and placebo (black bars) groups at the beginning and eplacebo group by paired t test, P 0.001. RBC, red blood cell.There was a very low prevalence of iodine deficiency asessed with standard indicators of iodine deficiency (uri-ry iodine excretion level 20 g/L, T3 level 1.08ol/L, and TSH 0.17 mIU/L) in these schoolchildren.fect of daily intake of micronutrientsResults for various biochemical parameters at baselined after supplementation are presented in Figs. 1 to 11.Among the hematopoietic micronutrients tested, a sig-cant net change was observed only with respect to folated vitamin A (Figs. 1, 2, 7, and 8). Supplementation had nonificant effect in improving mean hemoglobin in theplement or placebo group (Figs. 1 and 7). Althoughan serum ferritin levels in both groups were comparablebaseline, concentrations decreased in both groups at thed of the treatment period. However, this decrease was notnounced in children who received the supplement andal levels were significantly higher compared with those inplacebo group. When pooled data from each group ofildren who were anemic at baseline were considered, finalan hemoglobin concentration was significantly higher insupplement group than in the placebo group (Fig. 3).Daily intake of a micronutrient-enriched beverage regis-ed significant increases in RBC folate status (Fig. 1) andsma vitamin A and C levels (Fig. 2). Increments in RBCC folate. Bars represent the pooled mean standard deviation of the4 mo of supplementation. ***Supplement group is significantly differentassnanmEfannifiansigsupmeatenprofinthechmetheterfolcangroplapleplalevmeprodidencogroFigplapaiFigmehadS18 B. Sivakumar et al. / Nutrition 22 (2006) S15S25ate status (Fig. 7) and vitamin A (Fig. 8) were signifi-tly higher in the supplement group than in the placeboup and were uniform across grades 1 to 10. Althoughsma vitamin B12 status (Fig. 1) was higher in the sup-ment group, it did not significantly differ from that in thecebo group. The increment seen in vitamin C and B12els over the study period was not confined to the treat-. 2. Initial and final levels of plasma vitamin A and vitamin C. Bars represcebo (black bars) groups at the beginning and end of 14 mo of supplemered t test, P 0.001.. 3. Mean hemoglobin levels in children with anemia (120 g/L) and thosan standard deviation of supplement (white bars) and placebo (black baranemia and received supplement were significantly different from those who rent group because the placebo group also registered im-vement (Fig. 7).Zinc supplementation at 15% of Codex in the beveragenot increase plasma zinc levels (Fig. 4). Functionalzyme status representing vitamins B1, B2, and B6 wasmparable at baseline between the supplement and placeboups (Figs. 5 and 9). After supplementation, vitamin B2pooled mean standard deviation of the supplement (white bars) and***Supplement group is significantly different from placebo group byut anemia (120 g/L) before and after supplementation. Bars represents at the beginning and end of 14 mo of supplementation. Children whoe withos) groupent thentation.ceived placebo by t test, P 0.05.andeHocangroboFigpooplameFig bars) adev f 14 modiff rase actTKS19B. Sivakumar et al. / Nutrition 22 (2006) S15S25d B6 statuses improved dramatically as reflected by acrease in enzyme activity coefficients in both groups.wever, improvement in vitamin B2 status was signifi-tly greater in the supplement group than in the placeboup. In contrast, vitamin B1 status remained similar inth groups at the beginning and end of the study period.. 4. Plasma zinc in supplemented and placebo groups. Bars representled mean standard deviation of the supplement (white bars) andcebo (black bars) groups at the beginning and end of 14 mo of supple-ntation.. 5. Initial and final levels of vitamins B1, B2, and B6 in supplement (whiteiation of the supplement and placebo groups at the beginning and end oerent from placebo group by paired t test. AAT-AC, aspartate aminotransfe-AC, transketolase activation coefficient.There were no significant differences in values of serumcium, phosphorous, and PTH at baseline. At the end ofstudy, plasma PTH was significantly lower in the sup-ment group. Supplementation significantly increasedsma vitamin D levels in the supplement group at the endthe study despite lower mean levels at the start of thedy compared with the placebo group (Fig. 6). The mag-udes of improvement were in opposite directions withpect to plasma PTH and vitamin D, lower and higherth supplementation, respectively (Fig. 10).There was no inadequacy of iodine in these schoolchil-n. Mean concentrations of T3 and TSH did not differtween groups at baseline or after the study period. Excre-n of iodine in urine was significantly lower in the placeboup than in the supplement group at baseline. Both groupswed adequate excretion of iodine (50 g/L of urine).e decrease in TSH values in the supplement group wasnificant compared with the placebo group (Fig. 11).Mean urinary excretion of riboflavin at the end of thedy was higher in the supplement group (0.47 0.26/mL, n 113) than in the placebo group (0.26 0.17/mL, n 131).nd placebo (black bars) groups. Bars represent pooled mean standardof supplementation. ***P 0.001, supplement group is significantlyivation coefficient; GR-AC, glutathione reductase activation coefficient;calthepleplaofstunitreswidrebetiogroshoThsigstuggDiprocretietoexiropuicaingdeido[39vitcogiedevealeheIndthawaFig bars) adev f 14 modiff , parathS20 B. Sivakumar et al. / Nutrition 22 (2006) S15S25scussionOver the past four to five decades, the prevalence oftein-energy malnutrition, beriberi, and scurvy has de-ased in India with improvement in overall health facili-s [37]. However, micronutrient malnutrition, also referredas hidden hunger, remains a widespread problem. Forample, in the National Nutrition Policy, deficiencies ofn, iodine, and vitamin A were considered to be of graveblic health importance because they cause impaired phys-l and mental development, particularly in young, grow-children [38]. There have also been sporadic reports officiencies of other micronutrients such as riboflavin, pyr-xine, and folic acid in pregnant women and children]. Although the prevalence of clinical signs of iron andamin deficiencies has decreased, iron deficiency anemiantinues to be a major problem. Among the many strate-s suggested to control the prevalence of micronutrientficiency, fortification of food(s) with micronutrients is ary practical and effective strategy.The present results show surprising facts about the prev-nce of subclinical micronutrient deficiency in otherwisealthy Indian children who live in semi-urban areas ofia with adequate food intake.Pooled baseline results using standard cutoffs suggestt the prevalence of anemia (hemoglobin level 120 g/L). 6. Initial and final levels of indicators of bone health in supplement (whiteiation of the supplement and placebo groups at the beginning and end oerent from placebo group by paired t test (Final) and t test (Initial). PTHs as high as 54% in conjunction with widespread defi- pancies of folic acid (98%), vitamins B2 and B6 (65%),amin A (44%), vitamin B12 (40%), and vitamin D (22%).is finding is in agreement with previous reports from thision and elsewhere in India for deficiencies of somecronutrients [5,14].Micronutrient supplementation did not increase hemo-bin levels and substantially improve storage iron (plasmaritin), even though 100% of the Codex recommendedtary allowances (RDAs) for vitamin B12, folic acid, andamin C and 50% of the Codex RDA for vitamin Aportant micronutrients that assist in iron absorption)re given in addition to iron.Plasma ferritin concentrations decreased in both groupser the course of the study. This effect is paradoxicalcause a decrease did occur in supplement group, evenugh the decrease was less. Increased serum ferritin con-trations at baseline may have been due to infections.wever, the contribution of this factor is unlikely becausedecrease in ferritin was seen progressively over thetire study period (14 mo) and such a prolonged effectnot be attributed to infection. In addition, the childrenre apparently normal and did not have obvious undernu-ion. However, they had severe micronutrient deficiencybaseline. Anttila and Siimes [40] suggested that a de-ase in ferritin is an adaptive response reflecting increasedn utilization for tissue growth, and this process may bend placebo (black bars) groups. Bars represent pooled mean standardof supplementation. ***P 0.001, supplement group is significantlyyroid hormone.cievitThregmigloferdievit(imweovbethocenHotheencanwetritatcreirorticularly important during adolescence in boys and girls.MoheloncieFigplabloFigpoobarfromS21B. Sivakumar et al. / Nutrition 22 (2006) S15S25reover, an Indonesian study [10] associated a lack ofmoglobin response to supplementation with iron withg-term undernutrition and multiple micronutrient defi-ncies.. 7. Changes in levels of hematopoietic micronutrients (final minus initiacebo (black bars) groups. ***P 0.001, supplement group is significantlyod cell.. 8. Changes in levels of vitamin A (final minus initial). Bars representled mean difference of the supplement (white bars) and placebo (blacks) groups. ***P 0.001, supplement group is significantly differentonplacebo group by paired t test. 1 to 9, grades 1 to 9.The effect of supplementation on RBC folate and plasmaamin B12 level was very positive. However, this did notult in improved hemoglobin to any significant extent,gesting that the cause for anemia in these children wasinly due to lack of iron. The question of compliance toverage intake during a vacation was verified by measur-urinary riboflavin. The supplement group had highercretion levels, suggesting that the children had consumedsupplement. The chances of possible worm infestationding to anemia were negligible in the present studycause all subjects were dewormed before initiation andring the supplementation period. The other possibility ist the milk protein present in the drink could have che-ed some of the non-heme iron in the drinks and thusuenced its absorption. It may also be that the amount ofn (14 mg) provided through the supplement was insuffi-nt to meet the childrens requirements, which is highern the amount in the Codex RDA. The Indian RDA forn for children 6 to 16 y of age is 19 to 41 mg/d [41].wever, when the same data were stratified according tose who had anemia at baseline, a statistically significantprovement in hemoglobin was seen after supplementationcomparison with placebo. Thus, improvement occurredrepresent pooled mean difference of the supplement (white bars) andnt from placebo group by paired t test. 1 to 9, grades 1 to 9; RBC, redvitressugmabeingextheleabeduthalatinflirociethairoHothoiminl). Barsdifferely when there was a pre-existing deficiency of micronu-trieciedemePTplaplesensupretchintweiodfinofprelevwhFiggroamS22 B. Sivakumar et al. / Nutrition 22 (2006) S15S25nts and this has been well established with iron defi-ncy anemia.No direct changes in plasma calcium were expectedspite 50% of the Codex RDA (400 mg) being supple-nted daily. However, there was a significant decrease inH levels of the supplement group compared with thecebo group, which can be considered an effect of sup-mentary calcium. As expected, 25OH D3 levels repre-ting vitamin D status also improved significantly in theplement group; all of these promote increased calciumention. It is not clear whether this was a reflection of theanges taking place in the body (drawing more mineralo the bone) because total bone area and muscle massre increased in the supplemented children [42].There was no difference in incremental values of urinaryine or associated hormones except suppression in theal TSH level in the supplement group. The adequate levelexcretion of iodine is in tune with the lower goitervalence noted in these children [43]. The change in TSHel may be a reflection of the improved iodine status,. 9. Changes in levels of B vitamins (final minus initial). Bars represent poups. ***P 0.001, supplement group is significantly different from pinotransferase activation coefficient; GR-AC, glutathione reductase activaich in turn would improve hormone synthesis. stuB-complex vitamins such as B1, B2, and B6 usually occurfood together and have parallel effects on psychomotorction. The present results showed that there was a signifi-t prevalence of vitamin B2 and B6 deficiencies at baseline.wever, supplementation had a differential effect on thetus of vitamins B2 and B6. Although levels of B2 improvednificantly, B6 levels showed a variation over the studyiod (from 65% to 12%), although supplementation for bothamins was 100% of the Codex RDA. Such fluctuations inamin B6 levels may be due to seasonal changes in intake oruirements. However, vitamin B1 levels in both groups re-ined unchanged. Because supplementation of vitamin B1s at 50% of the Codex RDA, it can be argued that fortifi-ion at 50% of the RDA (0.7 mg) is inadequate. However,level of inadequacy at baseline did not support this notion.s very important to provide adequate dietary intake of B1,and B6 vitamins in children because the inadequacy ofse vitamins has been associated with decreased psychomo-function in children [5,9]. When assessing the effect ofcronutrient supplementation on mental function, the presentean difference of the supplement (white bars) and placebo (black bars)group by paired t test. 1 to 9, grades 1 to 9; AAT-AC, aspartatefficient; TK-AC, transketolase activation coefficient.infuncanHostasigpervitvitreqmawacattheIt iB2thetormioled mlacebotion coedy indicated that the attention-concentration scores of theKnthezinoflowRDstasuplochamimaworecthedrecrofacotheraFigbarS23B. Sivakumar et al. / Nutrition 22 (2006) S15S25ox Cube Test were higher in the supplement group than inplacebo group [44].There was no inadequacy of zinc as assessed by plasmac concentration. This could be due to the poor sensitivityplasma zinc concentration to reflect zinc status and thelevel of zinc supplementation of 15% of the zinc CodexI, which could not have made any difference to zinctus. The reason for limiting the amount of zinc in theplement to 15% of the Codex RDI was to conform to theal regulatory requirement.It is also worth mentioning that the present results wouldve been more amplified if the placebo had not been not alk-based malted beverage because the milk and otherlted ingredients inherently contain micronutrients, whichuld have conferred some beneficial effect to the placeboipients, thereby decreasing the actual difference betweensupplement and placebo groups.Many of the studies conducted previously in Indian chil-n have shown that the state of health, particularly mi-nutrient deficiency of schoolchildren, is far from satis-tory despite the fact that school health programs ander nutritional programs have been in operation for sev-. 10. Changes in levels of indicators of bone health (final minus initial). Bars res) groups. ***P 0.001, supplement group is significantly different from plapresent pooled mean difference of the supplement (white bars) and placebo (blackcebo group by paired t test. 1 to 9, grades 1 to 9; PTH, parathyroid hormone.Fig. 11. Changes in levels of TSH (final minus initial). Bars representpooled mean difference of the supplement (white bars) and placebo (blackbars) groups. ***P 0.001, supplement group is significantly differentfrom placebo group by paired t test. 1 to 9, grades 1 to 9; TSH, thyroid-l decades [3941]. However, most of these studies were stimulating hormone.carchdewhcli80ciuRDcroThgrosupCoshosucantheplegrepaAcBhSedeFoRe[1[2[3[4[5[6[7[8[9[10[11[12[13[14[15[16[17[18[19[20[21[22[23[24[25[26[27[28[29S24 B. Sivakumar et al. / Nutrition 22 (2006) S15S25ried out in rural areas and in essentially malnourishedildren with clinical signs and symptoms of micronutrientficiency. In contrast, the present study evaluated subjectso were apparently normal and healthy children with nonical signs of deficiency. The diet provided, on average,% of energy requirements. Intakes of protein, fat, cal-m, folic acid, and vitamin C were adequate as per theA for Indians [43]. The diet was limiting in some mi-nutrients such as iron, thiamin, niacin, and vitamin A.e only difference between the placebo and supplementups was the additional micronutrient provided in theplement.nclusionDaily intake of a micronutrient-enriched beveragewed a significant positive shift in the status of nutrientsh as vitamins A, C, B2, and B12, folic acid, vitamin D,d calcium across the age groups of 6 to 16 y, indicatingefficacy of this approach in correcting biochemical de-tion of multiple micronutrients. Thus, there is clearly aater need for micronutrient supplementation even in ap-rently normal healthy children.knowledgementsThe authors are grateful for the expert advice of P.askaram, M.D., A. 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Sivakumar et al. / Nutrition 22 (2006) S15S25Effect of micronutrient supplement on health and nutritional status of schoolchildren: biochemical statusIntroductionMaterials and methodsStatistical analysisResultBaselineEffect of daily intake of micronutrientsDiscussionConclusionAcknowledgementsReferences

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