Abstract
Background/Objectives:
In India, approx. 70% of the adolescent girls are anaemic (haemolgobin <120 g/l). The present study was a supervised randomised double-blind clinical trial conducted among adolescent girls (11–18 years) to assess and compare the impact of weekly iron folic acid (IFA) supplementation with or without vitamin B12 on reduction in the prevalence of anaemia and on blood/serum levels of haemoglobin, serum ferritin, folic acid and vitamin B12.
Subjects/Methods:
Community-based randomized controlled trial was carried out in Kirti Nagar slums of West Delhi. A total of 446 mild (100–119 g/l) and moderate (70–99 g/l) anaemic volunteer adolescent girls were identified and randomised into two groups. Weekly supervised supplementation was given for 26 weeks: Group A (n=222): iron (100 mg), folic acid (500 mcg) and placebo; Group B (n=224): iron (100 mg), folic acid (500 mcg) and cyanocobalamin (500 mcg for 6 weeks and 15 mcg for 20 weeks). Haemoglobin, serum ferritin, folic acid and vitamin B12 levels were assessed at baseline and after intervention. A total of 373 subjects completed 26 weeks of supplementation successfully.
Results:
The mean haemoglobin increased from 106.7±11.2 g/l and 108.9±8.91 g/l in Group A and Group B at baseline to 116.4±10.8 g/l (P<0.001) and 116.5±10.26 g/l (P<0.001) at post-intervention, respectively, with the reduction in the prevalence of anaemia by 35.9% in Group A and 39.7% in Group B (P>0.05). A total of 63.3% participants had deficient vitamin B12 levels (<203 pg/ml) at baseline, which reduced to 40.4% after intervention with cyanocobalamin, whereas no change was observed in vitamin B12 status in the other group. Significant reduction (P=0.01) in the prevalence of serum ferritin deficiency (<15 ng/ml) was observed in the group supplemented with vitamin B12 (from 36.5 to 6.4%) as compared with the other group supplemented with only IFA (from 39.1 to 15.2%).
Conclusions:
IFA supplementation with or without vitamin B12 is an effective measure to cure anaemia. Although addition of vitamin B12 had similar impact on improving haemoglobin status as IFA alone, it resulted in better ferritin status. Hence, more multi-centre studies with a longer duration of supplementation or higher dose of vitamin B12 may be undertaken to assess the possible impact of vitamin B12 on improving haemoglobin levels in the population.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
UNICEF. Prevention and Nutritional Anaemia: A South Asia Priority United Nations Children’s Fund. Regional Office for South Asia, 2002.
Toteja GS, Singh P, Dhillon BS, Saxena BN, Ahmed FU, Singh RP et al. Prevalence of anemia among pregnant women and adolescent girls in 16 districts of India. Food Nutr Bull 2006; 27: 311–315.
National Family Health Survey 3 India 2005-2006; International Institute of Population Sciences: Mumbai, India and ORC Macro, Calverton, MD, USA, 2007.
District Level Household Survey 2007-2008, Available from http://www.rchindia.org/dlhs_india.htm. (accessed on 15 March 2014.
NNMB Technical Report No. 22. National Nutrition Monitoring Bureau (NNMB) Prevalence of Micronutrient Deficiencies. National Institute of Nutrition, Indian Council of Medical Research: Hyderabad, India, 2003.
NNMB Technical Report No. 24. National Nutrition Monitoring Bureau (NNMB) Prevalence of Micronutrient Deficiencies. National Institute of Nutrition, Indian Council of Medical Research: Hyderabad, India, 2006.
Guidelines for Iron Folic Acid Supplementation. Ministry of Health and Family Welfare, Government of India: India, 2007.
Guidelines for Control of Iron Deficiency Anaemia National Iron+Initiative. Adolescent Division, Ministry of Health and Family Welfare, Government of India: India, 2013. Available from: http://www.unicef.org/india/10.National_Iron_Plus_Initiative_Guidelines_for_Control_of_IDA.pdf.
Fishman SM, Christian P, West KP . The role of vitamins in the prevention and control of anaemia. Public Health Nutr 2000; 3: 125–150.
Chanarin I, Deacon R, Lumb M, Perry J . Cobalamin-folate interrelations. Blood Rev 1989; 3: 211–215.
Penninx BW, Guralnik JM, Ferrucci L, Fried LP, Allen RH, Stabler SP . Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the women's health and aging study. Am J Psychiatry 2000; 157: 715–721.
Spray GH, Witts LJ . The utilization of folic acid given by mouth. Clin Sci 1952; 3: 273–281.
Cox EV, Meynell MJ, Cooke WT, Gaddie R . Folic acid and cyanocobalamin in pernicious anaemia. Clin Sci 1958; 17: 693–699.
Watanabe F . Vitamin B12 sources and bioavailability. Exp Biol Med 2007; 232: 1266–1274.
Allen LH . Iron supplements: Scientific issues concerning efficacy and implications for research and programs. J Nutr 2002; 132: 813S–819S.
Zwart A, van Assendelft OW, Bull BS, England JM, Lewis SM, Zijlstra WG . ICSH Recommendations for reference method for hemoglobinometry in human blood (ICSH standards 1995) and specifications for international hemoglobincyanamyde standard. J Clin Pathol 1996; 49: 271–274.
WHO. Worldwide prevalence of anaemia: 1993–2005. WHO Global Database on Anaemia, 2008. Available from http://whqlibdoc.who.int/publications/2008/9789241596657_eng.pdf.
Kotecha PV, Nirupam S, Karkar PD . Adolescent girls’ anaemia control programme, Gujarat, India. Indian J Med Res 2009; 130: 584–589.
Deshmukh PR, Garg BS, Bharambe MS . Effectiveness of weekly supplementation of Iron to control anaemia among adolescent girls of Nashik, Maharashtra, India. J Health Popul Nutr 2008; 26: 74–78.
Vir SC, Singh N, Nigam AK, Jain R . Weekly iron and folic acid supplementation with counseling reduces anemia in adolescent girls: a large-scale effectiveness study in Uttar Pradesh, India. Food Nutr Bull 2008; 29: 186–194.
Chakma T, Vinay Rao P, Meshram PK . Factors associated with high compliance/feasibility during iron and folic acid supplementation in a tribal area of Madhya Pradesh, India. Public Health Nutr 2012; 28: 1–4.
Dongre AR, Deshmukh PR, Garg BS . Community-led initiative for control of anemia among children 6 to 35 months of age and unmarried adolescent girls in rural Wardha, India. Food Nutr Bull 2011; 32: 315–323.
Patel BH, Saxena D, Singhal D, Sharma VK, Maheshwari RS, Prakash MM . Intervention of iron-folic acid in school children. J Hum Ecol 2009; 25: 61–62.
Agarwal KN, Gomber S, Bisht H, Som M . Anemia prophylaxis in adolescent school girls by weekly or daily. Indian Pediatr 2003; 40: 296–301.
Shobha S, Sharda D . Efficacy of twice weekly iron supplementation in anaemic adolescent girls. Indian Pediatr 2003; 40: 1186–1190.
Joshi M, Gumashta R . Weekly iron folate supplementation in adolescent girls–an effective nutritional measure for the management of iron deficiency anaemia. Glob J Health Sci 2013; 5: 188–194.
Casey GJ, Phuc TQ, MacGregor L, Montresor A, Mihrshahi S, Thach TD et al. A free weekly iron-folic acid supplementation and regular deworming program is associated with improved hemoglobin and iron status indicators in Vietnamese women. BMC Public Health 2009; 9: 261–268.
Tee ES, Kandiah M, Awin N, Chong SM, Satgunasingam N, Kamarudin L et al. School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent girls. Am J Clin Nutr 1999; 69: 1249–1256.
Cairo G, Ronchi R, Buccellato FR, Veber D, Santambrogio P, Scalabrino G . Regulation of the ferritin H subunit by vitamin B12 (cobalamin) in rat spinal cord. J Neurosci Res 2002; 69: 117–124.
Duggan C, Srinivasan K, Thomas T, Samuel T, Rajendran R, Muthayya S et al. Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status. J Nutr 2014; 144: 758–764.
Shahab-Ferdows S, Anaya-Loyola MA, Vergara-Castañeda H, Rosado JL, Keyes WR, Newman JW et al. Vitamin B-12 supplementation of rural Mexican women changes biochemical vitamin B-12 status indicators but does not affect hematology or a bone turnover marker. J Nutr 2012; 142: 1881–1887.
Iyengar L, Apte SV . Prophylaxis of anaemia in pregnancy. Am J Clin Nutr 1970; 23: 725–730.
Basu RN, Sood SK, Ramachandran K, Mathur M, Ramalingaswami V . Etiopathogenesis of nutritional anemia in pregnancy: a therapeutic approach. Am J Clin Nutr 1973; 26: 591–594.
Sood SK, Ramachandran K, Mathur M, Gupta K, Ramalingaswamy V, Swarnabai C et al. The effects of supplemental oral iron administration to pregnant women. Q J Med 1975; 44: 241–258.
Reid ED, Lopez P, Galaviz IA, Isoard F, Rosado JL, Allen LH . Hematological and biochemical responses of rural Mexican preschoolers to iron alone or iron plus micronutrients. FASEB J 2001; 15: A731 (abstract).
Chandelia S, Chandra J, Narayan S, Aneja S, Chawla HM, Sharma S et al. Addition of cobalamin to iron and folic acid improves hemoglobin rise in nutritional anemia. Indian J Pediatrics 2010; 12: 1592–1596.
Green R . Indicators for assessing folate and vitamin B-12 status and for monitoring the efficacy of intervention strategies. Am J Clin Nutr 2011; 94: 666S–672S.
Klee GG . Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B12 and folate. Clin Chem 2000; 46: 1277–1283.
Yetley EA, Pfeiffer CM, Phinney KW, Bailey RL, Blackmore S, Bock JL et al. Biomarkers of vitamin B-12 status in NHANES: a roundtable summary. Am J Clin Nutr 2011; 94: 313S–321S.
Green R . Indicators for assessing folate and vitamin B12 status and for monitoring the efficacy of intervention strategies. Food Nutr Bull 2008; 29: S52–S63.
Yetley EA, Pfeiffer CM, Phinney KW, Fazili Z, Lacher DA, Bailey RL et al. Biomarkers of folate status in NHANES: a roundtable summary. Am J Clin Nutr 2011; 94: 303S–312S.
WHO. Iron Deficiency Anaemia Assessment, Prevention, and Control. A guide for programme managers, 2001. WHO/NHD/01.3.
de Benoist B . WHO: Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 2008; 29: S238–S244.
Acknowledgements
The critical inputs given by members of Data Safety Monitoring Board (Dr Padam Singh, Dr HPS Sachdev and Dr Kumud Khanna) are acknowledged. Drug Controller General of India and State Licensing Authority, Bhopal, are deeply acknowledged for granting permission to manufacture the supplements and permission to conduct the trial. Sincere thanks to Director General, ICMR, for granting Senior Research Fellowship to the first author for carrying out the work as part of PhD and for providing facility for biochemical analysis. The authors are thankful to M/s Cyano Pharma Private Limited, Indore (Madhya Pradesh), for providing supplements required for the trial.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Bansal, P., Toteja, G., Bhatia, N. et al. Impact of weekly iron folic acid supplementation with and without vitamin B12 on anaemic adolescent girls: a randomised clinical trial. Eur J Clin Nutr 70, 730–737 (2016). https://doi.org/10.1038/ejcn.2015.215
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ejcn.2015.215