EFFECT OF VITAMIN B12 SUPPLEMENT ON SERUM LEVELS OF VITAMIN B12 AND MEMORIZING ABILITY ON PRESCHOOL CHILDREN
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1 IJPSR (2018), Volume 9, Issue 10 (Reserch Article) Received on 12 Jnury, 2018; received in revised form, 05 June, 2018; ccepted, 13 July, 2018; published 01 October, 2018 EFFECT OF VITAMIN B12 SUPPLEMENT ON SERUM LEVELS OF VITAMIN B12 AND MEMORIZING ABILITY ON PRESCHOOL CHILDREN Zulhid Lubis *, Hrdinsyh, Syrif Hidyt, Fsli Jl nd Muhill Fculty of Public Helth of University of North Sumtr, Medn, Indonesi. Keywords: Memorizing bility, Vitmin B12 supplementtion, Preschool children Correspondence to Author: Zulhid Lubis Fculty of Public Helth of University of North Sumtr, Medn, Indonesi. E-mil: INTRODUCTION: According to Ickowitz et l., 1 stte tht Indonesi is fcing multitude of food security nd nutrition chllenges. Despite considerble progress over the lst few decdes in reducing child mortlity nd the prevlence of underweight nd stunted children, there remins long wy to go before ll Indonesin children re free of mlnutrition. Over single decde, from the period to , child mortlity in Indonesi dropped by 33% from 69 to 44 child deths per 1,000 live births, yet the prevlence of stunting in children under 5 yers of ge remins high t 25.2% nd 39.2%, in urbn nd rurl res respectively. Vitmin B12 deficiency cn ffect individuls t ll ges, but most prticulrly elderly individuls. QUICK RESPONSE CODE ABSTRACT: This reserch imed to nlyze the effect of vitmin B12 supplementtion on vitmin B12 serum level nd memorizing bility of preschool children. A community - rndomized controlled tril of 29 preschool children (4-6 yer) ws conducted for six months. Subjects were divided into two groups, tretment group (received 10 mcg of vitmin B12 dily syrup) nd control group (plcebo). Serum vitmin B12 nd memory levels of children were mesured before nd fter the intervention. Result of reserch ws fter 6 months of vitmin B12 on supplementtion prevlence of vitmin B12 deficiency decresed in tretment group from 26.7% to 0.0%, while in the control group incresed from 21.4% to 28.6%. The men of incresing serum vitmin B12 ws significntly different mong those groups (148 ± pg/ml in the tretment group nd 3.7 ± 12.8 pg/ml in the control group). Memorizing bility ffected by vitmin B12 supplementtion for overll children with reltive risk (RR) ws Reviews of this reserch imply the importnt result of vitmin B12 supplementtion on improving vitmin B12 nd memory levels of preschool children. DOI: /IJPSR (10) Article cn be ccessed online on: DOI link: Infnts, children, dolescents nd women of reproductive ge re lso t high risk of deficiency in popultions where dietry intke of B12- contining niml-derived foods is restricted. Deficiency is cused by either indequte intke, indequte biovilbility or mlbsorption 2. The Low vitmin B12 sttus is ttributed to vegetrinism in these popultions. It is not known whether low B12 sttus is ssocited with metbolic risk of the offspring in whites, where the childhood metbolic disorders re incresing rpidly 3. Another study suggests tht poor vitmin B12 sttus in infncy is linked to poor growth nd neurodevelopment. Brin development strts from conception, nd pregnncy is period of rpid growth nd development for the brin 4. Vitmin B12 is only synthesized by certin bcteri nd humns obtin it from niml source foods such s met, diry, eggs, nd fish 5 ; which explins why children who rrely et these foods re expectedly t risk of vitmin B12 deficiency. Interntionl Journl of Phrmceuticl Sciences nd Reserch 4436
2 In group which is llegedly t high risk of vitmin B12 deficiency re the children from poor fmilies due to low purchsing bility for niml source food. Relted to the importnt function of vitmin B12 in cognitive development, n experimentl study is necessry s n lterntive effort to improve vitmin B12 sttus nd simultneously improve cognitive development of children. This study imed to nlyze the effect of vitmin B12 supplementtion on vitmin B12 serum nd memory level in preschool children. METHODS: This experimentl study ws conducted using Community - Rndomized Control Tril" design study. The design includes n initil period in which no clusters re exposed to the intervention. Subsequently, t regulr intervls (the steps ) one cluster (or group of clusters) is rndomized to cross from the control to the intervention under evlution. This process continues until ll clusters hve crossed over to be exposed to the intervention. At the end of the study there will be period when ll clusters re exposed. Dt collection continues throughout the study, so tht ech cluster contributes observtions under both control nd intervention observtion periods 6. Subjects were preschoolers (4-6 yers) in Kindergrten (TK) Al-Zhr district of Bogor in 2007, 15 children were in the tretment group nd 14 children were in the control group. The tretment group received vitmin B12 syrup (glucose syrup contins vitmin B12) t dose of 10 mg/dy in 2.5 ml syrup. The control group ws given plcebo syrup mde from the sme ingredient with the glucose syrup but without vitmin B12). The intervention ws given every dy for 6 months, smple syrups were given t school from Mondy to Fridy, while on Sturdy nd Sundy they were being given t home. Serum vitmin B12 levels were mesured by the AxSYM method (Abbott Lbortories, USA, 2005) performed two times t the beginning nd the end of the intervention t the Lbortory Pondok Indh Hospitl in Jkrt. Vitmin B12 sttus is determined by vitmin B12 serum levels. The deficiency ws condition when serum vitmin B12 <300 pg/ml, norml ws when vitmin B12 serum levels 300 pg/ml. Memorizing ech child ws mesured by memorizing picture method. The child ws showed picture for 0, 5 min. Every picture hs its score. This method ws performed t the beginning nd t the end of the intervention. The score ws bsed on the picture size, nmely: score for lrge size imge ws 3, for the medium size ws 5, for the smll size ws 7, nd for extr smll size ws 9. Dt nlysis ws performed with different test Independent, Smple T Test, to determine the difference in level of vitmin B12 serum nd the difference in scores of memorizing bility in both groups. Furthermore, to nlyze the effect of vitmin B12 supplementtion on vitmin B12 serum levels nd memorizing bility of children, logistic regression test ws performed. RESULT: Serum levels of vitmin B12 nd Vitmin B12 Sttus: The verge serum vitmin B12 levels in the beginning of intervention ws lmost the sme in both groups: 337 ± 62.8 pg/ml in the tretment group nd ± 83.2 pg/ml in the control group Tble 1. Sttisticl nlysis showed tht there ws no significnt difference between the two groups t the strt of the intervention (p>0.5). But fter six months, the verge vitmin B12 serum levels of the tretment group incresed by ± pg/ml. While the verge vitmin B12 serum level in the control group incresed by 3.7 ± 12.8 pg/ml. Sttisticl nlysis showed significnt difference in the levels of vitmin B12 serum between the tretment group nd the control group (p = 0.009). The difference ws even more pronounced with the test of difference, which showed tht difference or chnge of serum vitmin B12 levels ws significnt with p = TABLE 1: AVERAGES SERUM LEVELS OF VITAMIN B12 Time Vitmin B12 levels (pg/ml) Sig. mesurement Tretment (n=15) Control (n=14) Totl (n=29) Beginning ± ± ± End ± ± ± Difference ± ± ± = significntly different (p<0.05) Interntionl Journl of Phrmceuticl Sciences nd Reserch 4437
3 The increse in serum levels of vitmin B12 in the tretment group ws followed by the improvement of the sttus of vitmin B12. At the beginning of the study, there were 26.7% of the children hve Vitmin B12 deficiency in the tretment group nd 21.4% in the control group. After 6 months of Vitmin B12 supplementtion, the prevlence of Vitmin B12 deficiency in the tretment group decresed to 0.0%, which mens there were no children with vitmin B12 deficiency in the tretment group t the end of the intervention Fig. 1. Wheres in the control group, the prevlence of vitmin B12 deficiency incresed from 21.4% to 28.6% t the end of the intervention. FIG. 1: PERCENTAGE OF CHILDREN WITH VITAMIN B12 DEFICIENCY The Effect of vitmin B12 supplementtion on serum vitmin B12 levels ws nlyzed by liner regression test Tble 2. The results indicted tht vitmin B12 supplementtion hs significnt influence over serum levels of vitmin B12 (p = 0:03). This suggested tht the increse of level vitmin B12 levels in the tretment group occurred due to vitmin B12 supplements given for 6 months. R Squre rte of mens tht 28% of the vrince of serum levels of vitmin B12 occurred due to 6 months vitmin B12 supplementtion. TABLE 2: REGRESSION TEST RESULTS SERUM LEVELS OF VITAMIN B12 Vribles R Squre B T Sig. Constnts Vit. B12 supplementtion (0=control; 1=tretment) = significnt effect (p < 0.05) The Effect of vitmin B12 Supplements on Memorizing Ability: Children memorizing bility mesured by the 'memorizing picture' method presented s memorizing scores Tble 3. After 6 months vitmin B12 supplementtion, the verge of memorizing score improved, compred to score of memorizing before intervention to both the tretment group nd the control group. TABLE 3: MEAN SCORES ON THE CHILDREN MEMORIZING ABILITY Time Memorizing Score Sig. mesurement Tretment (n=15) Control (n=14) Totl (n=29) Beginning 26.5 ± ± ± End 40.2 ± ± ± Difference 13.7 ± ± ± = significntly different (p < 0.05) The increses of memorizing scores in the tretment group were higher t 13.7 ± 4.5 points compred to the control group t 9.1 ± 2.4. The test of difference result showed tht there were no significnt differences on memorizing scores before nd fter the intervention. Also, there were no differences of the verge of memorizing scores in both tretment group nd control group before nd fter the intervention. But the test of difference result showed tht there were differences (p = 0.002) of memorizing scores in the tretment group nd the control group. The effect of vitmin B12 supplementtion on memorizing bility ws nlyzed by logistic regression test. The test result showed tht there ws significnt effect of vitmin B12 supplementtion on children memorizing scores (p = 0.021). This indicted tht 6 month vitmin B12 supplementtion cn improve children memorizing scores in Tble 4. TABLE 4: LOGISTIC REGRESSION TEST RESULTS EFFECT OF VITAMIN B12 SUPPLEMENTS AGAINST MEMORY Vribles B Error Exp (B) Sig. Constnts Vit. B12 supplementtion (0=control; 1=tretment) = significnt effect ( p< 0.05 ) Interntionl Journl of Phrmceuticl Sciences nd Reserch 4438
4 The Exp (B) ws the vlue of the Reltive Risk (RR) mounted to 19,500, which indicted tht children who received vitmin B12 supplements would hve 19.5 times greter chnce of hving memorizing scores higher thn the verge, compred to children who did not receive Vitmin B12 supplements. DISCUSSION: The test result t the beginning of intervention (before vitmin B12 supplementtion) showed tht 26.7% preschool children were deficient in vitmin B12 in the tretment group nd 21.4% in the control group. The numbers were lower compred to reserch in Keny, which its prevlence of vitmin B12 deficiency 40 % of children in Keny 7. Poor Vitmin B12 sttus is common mong young children in mny low- to middle-income countries (LMIC) 8. According to Shipton nd Thchil 9 Vitmin B12 deficiency is common condition which cn present with nonspecific clinicl fetures, nd in severe cses with neurologicl or hemtologicl bnormlities. Although clssiclly cused by pernicious nemi, this condition now ccounts for minority of cses nd vitmin B12 deficiency occurs most often due to food-bound coblmin mlbsorption. The mjor risk fctor for developing vitmin B12 deficiency is the well-chrcterized utoimmune disese pernicious nemi, which is cused by lck of production of intrinsic fctor by gstric prietl cells tht is needed for the intestinl bsorption of vitmin B12 nd eventully leds to the development of nemi nd/or severe neurologicl symptoms. Pernicious nemi cn ffect people of ll ges, but its incidence rises with ge. Conservtive estimtes indicte tht pernicious nemi ffects 2-3% of individul s 65 yers of ge. In ddition, importnt risk fctors re gstrointestinl surgery, such s gstric bypss or removl of the terminl ileum, which compromise the bsorption of vitmin B12. However, in low-income countries, vitmin B12 deficiency is lrgely due to low intke of vitmin B12 rich foods of niml origin, but possibly lso to gstrointestinl infections nd infesttions, nd host-microbiot interctions 10. Giving vitmin B12 for 6 months (24 weeks) to preschool children my increse serum levels of vitmin B12 of ± pg/ml). Increse levels of serum vitmin B12 followed by reduction in the number of children with vitmin B12 deficiency, 26.7% of children could overcome the deficiency fter receiving the intervention. While in the control group, the percentge of children with deficiency incresed from 21.4% to 28.6% t the end of the intervention. Supplementry feeding for school children in the form of met g / h for one cdemic yer ws ble to reduce the prevlence of vitmin B12 deficiency until 16 percent (80.7% t the beginning of the intervention to 64.1% t the end intervention). Likewise, the provision of milk to school children ml/h reduced the prevlence of vitmin B12 deficiency bout 26 percent (71.6% t the beginning of the intervention to 45.1% t the end of the intervention). A Reserch conducted by Kennedy 11, the mny intervention studies tht hve involved dministering just folic cid ± Vitmins B12 nd/or B6, hve generted equivocl results. Similrly, whilst we hve some knowledge of the minimum levels of ech B vitmin required in order to prevent explicit deficiency relted diseses, we hve poor understnding of the negtive effects of levels of consumption tht lie bove the minimum, but under the optiml level of consumption for these vitmins. Another study by Duong 12 explined tht emerging evidence from observtionl studies in dults hs linked low vitmin B-12 intke with depression nd mood disorders. Moreover, Finklestein 13 stted tht A study in Turkey noted tht DNA dmge ws incresed in vitmin B-12-deficient (vitmin B-12: <200 pg/ml) children nd their mothers; however, intrmusculr coblmin injections significntly decresed DNA dmge in leukocytes of vitmin B-12-deficient children 9 d fter tretment (P<0.001). The increse of memorizing scores of preschool children who received vitmin B12 supple-menttion t 13.7, 4.5 points is higher thn children who did not receive the supplementtion t 9.1, 2.4 points. The test of difference in children memorizing score before the intervention indicted tht there is no significnt difference. Likewise, t the end of the intervention the verge memorizing scores were not significntly different between the two groups. But test of difference results indicted tht there ws no significnt differences (p=0.002) between scores in the intervention group nd the control group. Interntionl Journl of Phrmceuticl Sciences nd Reserch 4439
5 This ws supported by reserch of Gskins et l., 10 which stte tht there is reson to believe tht certin micronutrients such s folte nd vitmin B- 12 could positively influence reproductive success. Pretretment intkes of folte nd vitmin B-12 were relted to higher probbility of live birth mong women undergoing ART in the United Sttes. On the other hnd, elevted plsm homocysteine concentrtion is sensitive mrker to evlute vitmin B12 nd folte deficiency. Elevted circulting totl homocysteine (thcy) concentrtion is risk fctor for crdiovsculr disese. In ddition, HHcy in the elderly is strongly ssocited with depression, impired cognitive function nd dementi 14. Plsm homocysteine nd MMA were usully high due to low vitmin B12 nd folte. Furthermore, it ws sid tht orl supplementtion of vitmin B12 could lower plsm homocysteine nd methylmlonic cid (MMA) but hs not been ble to improve cognitive function. CONCLUSION: Vitmin B12 supplementtion to preschool children mde positive nd significnt effect on serum vitmin B12 levels, with n increse t 148.4, pg/ml. The increse of vitmin B12 serum levels ws lso followed by improvement of preschool children memorizing bility (the verge of score increse to 13.7, 4.5) Children who received vitmin B12 supplements for 6 months hd the opportunity to hve score of memory bove the verge of 19.5 times greter thn children who did not receive vitmin B12 supplements. Vitmin B12 supplementtion is suggested s n lterntive option to improve vitmin B12 sttus of preschool nd school children since mjority of children in Indonesi still lck of niml source foods (ASFs) s the source of vitmin B12. ACKNOWLEDGEMENT: Thnks go to the PT. Klbe Frm Indonesi tht hs helped provide vitmin B12 supplement for the purposes of this study. CONFLICT OF INTEREST: Nil REFERENCES: 1. Ickowitz A, Rowlnd D, Powell B, Slim MA nd Sunderlnd T: Forests, trees, nd micronutrient-rich food consumption in Indonesi. PloS one. 2016; 11(5): e Green R, Allen LH, Bjørke-Monsen AL, Brito A, Guént JL, Miller JW, Molloy AM, Nexo E, Stbler S, Toh BH nd Uelnd PM: Vitmin B 12 deficiency. Nture Reviews Disese Primers 2017; 3: Adiklkoteswri A, Vtish M, Lwson A, Wood C, Sivkumr K, McTernn PG, Webster C, Anderson N, Yjnik CS, Tripthi G nd Srvnn P: Low mternl Vitmin B12 sttus is ssocited with lower cord blood HDL cholesterol in white Cucsins living in the UK. Nutrients 2015; 7(4): Chndyo RK, Ulk M, Kvestd I, Shresth M, Rnjitkr S, Bsnet s, Hysing M, Shresth L nd Strnd TA: The effects of Vitmin B12 supplementtion in pregnncy nd postprtum on growth nd neurodevelopment in erly childhood: Study Protocol for Rndomized Plcebo Controlled Tril. BMJ Open. 2017; 7: e Zhng Y, Hodgson NW, Trivedi MS, Abdolmleky HM, Fournier M, Cuenod M, Do KQ nd Deth RC: Decresed brin levels of Vitmin B12 in ging, utism nd schizophreni. PLoS One. 2016; 11(1): e Hemming K, Hines TP, Chilton PJ, Girling AJ nd Lilford RJ: The stepped wedge cluster rndomised tril: rtionle, design, nlysis, nd reporting. BMJ. 2015; 350: h Herrán OF, Wrd JB nd Villmor E: Vitmin B 12 serosttus in Colombin children nd dult women: results from ntionlly representtive survey. Public helth nutrition 2015; 18(5): Kvestd I, Tnej S, Kumr T, Hysing M, Refsum H, Yjnik CS, Bhndri N nd Strnd TA: Folte nd Vitmin B12 Study Group. Vitmin B12 nd folic cid improve gross motor nd problem-solving skills in young north Indin children: A rndomized plcebo-controlled tril. Plos one 2015; 10(6): e Shipton MJ nd Thchil J: Vitmin B12 deficiency - A 21 st century perspective. Clin. Medicine 2015; 15(2): Kennedy DO: B Vitmins nd the brin: Mechnisms, dose nd efficcy-a review. Nutrients 2016; 8(2): Gskins AJ, Chiu YH, Willims PL, Ford JB, Toth TL, Huser R nd Chvrro JE: EARTH Study Tem. Assocition between serum folte nd Vitmin B-12 nd outcomes of ssisted reproductive technologies. The Americn journl of clinicl nutrition 2015; 102(4): Duong MC, Mor-Plzs M, Mrín C nd Villmor E: Vitmin B-12 Deficiency in Children Is Associted with Grde Repetition nd School Absenteeism, Independent of Folte, Iron, Zinc, or Vitmin A Sttus Biomrkers - 3. The Journl of nutrition 2015; 145(7): Finkelstein JL, Lyden AJ nd Stover PJ: Vitmin B-12 nd Perintl Helth 3. Advnces in Nutrition 2015; 6(5): Khodbndehloo N, Vkili M, Hshemin Z nd Zrdini HZ: Determining functionl Vitmin B12 deficiency in the elderly. Irnin Red Crescent Medicl Journl 2015; 17(8). How to cite this rticle: Lubis Z, Hrdinsyh, Hidyt S, Jl F nd Muhill: Effect of vitmin B12 supplement on serum levels of vitmin B12 nd memorizing bility on preschool children. Int J Phrm Sci & Res 2018; 9(10): doi: /IJPSR (10) All 2013 re reserved by Interntionl Journl of Phrmceuticl Sciences nd Reserch. This Journl licensed under Cretive Commons Attribution-NonCommercil-ShreAlike 3.0 Unported License. This rticle cn be downloded to ANDROID OS bsed mobile. Scn QR Code using Code/Br Scnner from your mobile. (Scnners re vilble on Google Plystore) Interntionl Journl of Phrmceuticl Sciences nd Reserch 4440
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