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A cost-effectiveness analysis of folic acid fortification policy in the United States

  • Tanya GK Bentley (a1), Milton C Weinstein (a2), Walter C Willett (a3) and Karen M Kuntz (a2)

To quantify the health and economic outcomes associated with changes in folic acid consumption following the fortification of enriched grain products in the USA.


Cost-effectiveness analysis.


Annual burden of disease, quality-adjusted life years (QALY) and costs were projected for four steady-state strategies: no fortification, or fortifying with 140, 350 or 700 μg folic acid per 100 g enriched grain. The analysis considered four health outcomes: neural tube defects (NTD), myocardial infarctions (MI), colon cancers and B12 deficiency maskings.


The US adult population subgroups defined by age, gender and race/ethnicity, with folate intake distributions from the National Health and Nutrition Examination Surveys (1988–1992 and 1999–2000), and reference sources for disease incidence, utility and economic estimates.


The greatest benefits from fortification were predicted in MI prevention, with 16 862 and 88 172 cases averted per year in steady state for the 140 and 700 μg fortification levels, respectively. These projections were between 6261 and 38 805 for colon cancer and 182 and 1423 for NTD, while 15–820 additional B12 cases were predicted. Compared with no fortification, all post-fortification strategies provided QALY gains and cost savings for all subgroups, with predicted population benefits of 266 649 QALY gained and $3·6 billion saved in the long run by changing the fortification level from 140 μg/100 g enriched grain to 700 μg/100 g.


The present study indicates that the health and economic gains of folic acid fortification far outweigh the losses for the US population, and that increasing the level of fortification deserves further consideration to maximise net gains.

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1. AE Czeizel & I Dudas (1992) Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 327, 18321835.

2.MRC Vitamin Study Research Group (1991) Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338, 131137.

3. LA Bazzano , K Reynolds , KN Holder & J He (2006) Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA 296, 27202726.

7. KM Koehler , SL Pareo-Tubbeh , LJ Romero , RN Baumgartner & PJ Garry (1997) Folate nutrition and older adults: challenges and opportunities. J Am Diet Assoc 97, 167173.

12. KL Tucker , B Mahnken , PW Wilson , P Jacques & J Selhub (1996) Folic acid fortification of the food supply. Potential benefits and risks for the elderly population [comment]. JAMA 276, 18791885.

16. DS Wald , NJ Wald , JK Morris & M Law (2006) Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. BMJ 333, 11141117.

17. LJ Williams , CT Mai , LD Edmonds , GM Shaw , RS Kirby , CA Hobbs , LE Sever , LA Miller , FJ Meaney & M Levitt (2002) Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United States. Teratology 66, 3339.

18. JA Tice , E Ross , PG Coxson , I Rosenberg , MC Weinstein , MG Hunink , PA Goldman , L Williams & L Goldman (2001) Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease: effect of grain fortification and beyond. JAMA 286, 936943.

19. PS Romano , NJ Waitzman , RM Scheffler & RD Pi (1995) Folic acid fortification of grain: an economic analysis. Am J Public Health 85, 667676.

21. SD Grosse , NJ Waitzman , PS Romano & J Mulinare (2005) Reevaluating the benefits of folic acid fortification in the United States: economic analysis, regulation, and public health. Am J Public Health 95, 19171922.

22. TGK Bentley , WC Willett , MC Weinstein & KM Kuntz (2006) Population-level changes in folate intake by age, gender, and race/ethnicity after folic acid fortification. Am J Public Health 96, 20402047.

27. L Williams , SA Rasmussen , A Flores , R Kirby & LD Edmonds (2005) Decline in the prevalence of spina bifida and anencephaly by race/ethnicity: 1995–2002. Pediatrics 116, 580586.

29. KM Anderson , PM Odell , PW Wilson & WB Kannel (1991) Cardiovascular disease risk profiles. Am Heart J 121, 293298.

35. AB Pedersen & J Mosbech (1969) Morbidity of pernicious anaemia. Incidence, prevalence, and treatment in a Danish county. Acta Med Scand 185, 449452.

36. EB Rimm , WC Willett , FB Hu , L Sampson , GA Colditz , JE Manson , C Hennekens & MJ Stampfer (1998) Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 279, 359364.

37. E Giovannucci , MJ Stampfer , GA Colditz , DJ Hunter , C Fuchs , BA Rosner , FE Speizer & WC Willett (1998) Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Intern Med 129, 517524.

40. SL Abby , IM Harris & KM Harris (1998) Homocysteine and cardiovascular disease. J Am Board Fam Pract 11, 391398.

43. DJ Cohen , DA Taira , R Berezin , DA Cox , MC Morice , GW Stone & CL Grines (2001) Cost-effectiveness of coronary stenting in acute myocardial infarction: results from the Stent Primary Angioplasty in Myocardial Infarction (Stent-PAMI) Trial. Circulation 104, 30393045.

44. RF Nease Jr, T Kneeland , GT O’Connor , W Sumner , C Lumpkins , L Shaw , D Pryor & HC Sox (1995) Variation in patient utilities for outcomes of the management of chronic stable angina. Implications for clinical practice guidelines. Ischemic Heart Disease Patient Outcomes Research Team. JAMA 273, 11851190.

45. KM Kuntz , KE Fleischmann , MGM Hunink & PS Douglas (1999) Cost-effectiveness of diagnostic strategies for patients with chest pain. Ann Intern Med 130, 709718.

46. RM Ness , AM Holmes , R Klein & R Dittus (1999) Utility valuations for outcome states of colorectal cancer. Am J Gastroenterol 94, 16501657.

47. JB Wong , FA Sonnenberg , DN Salem & SG Pauker (1990) Myocardial revascularization for chronic stable angina. Ann Intern Med 113, 852.

49. AL Frazier , GA Colditz , CS Fuchs & KM Kuntz (2000) Cost-effectiveness of screening for colorectal cancer in the general population. JAMA 284, 19541961.

50. RK Khandker , JD Dulski , JB Kilpatrick , RP Ellis , JB Mitchell & WB Baine (2000) A decision model and cost-effectiveness analysis of colorectal cancer screening and surveillance guidelines for average-risk adults. Int J Technol Assess Health Care 16, 799810.

51. F Loeve , ML Brown , R Boer , M van Ballegooijen , GJ van Oortmarssen & JD Habbema (2000) Endoscopic colorectal cancer screening: a cost-saving analysis. J Natl Cancer Inst 92, 557563.

52. RM Ness , AM Holmes , R Klein & R Dittus (2000) Cost-utility of one-time colonoscopic screening for colorectal cancer at various ages. Am J Gastroenterol 95, 18001811.

54. M Pignone , S Saha , T Hoerger & J Mandelblatt (2002) Cost-effectiveness analyses of colorectal cancer screening: a systematic review for the US Preventive Services Task Force. Ann Intern Med 137, 96104.

55. S Vijan , EW Hwang , TP Hofer & RA Hayward (2001) Which colon cancer screening test? A comparison of costs, effectiveness, and compliance. Am J Med 111, 593601.

57. M Werler , S Shapiro & A Mitchell (1993) Periconceptional folic acid exposure and risk of occurrent neural tube defects. JAMA 269, 12571261.

58. LE Daly , PN Kirke , A Molloy , DG Weir & JM Scott (1995) Folate levels and neural tube defects. Implications for prevention [comment]. JAMA 274, 16981702.

59. S Daly , JL Mills , AM Molloy , M Conley , YJ Lee , PN Kirke , DG Weir & JM Scott (1997) Minimum effective dose of folic acid for food fortification to prevent neural-tube defects. Lancet 350, 16661669.

60. NJ Wald , MR Law , JK Morris & DS Wald (2001) Quantifying the effect of folic acid. Lancet 358, 20692073.

62. R Carmel (1996) Prevalence of undiagnosed pernicious anemia in the elderly. Arch Intern Med 156, 10971100.

63. P Novakovic , JM Stempak , KJ Sohn & YI Kim (2006) Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis 27, 916924.

64. BF Cole , JA Baron , RS Sandler ; Polyp Prevention Study Group (2007) Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 297, 23512359.

65. B Van Guelpen , J Hultdin , I Johansson , G Hallmans , R Stenling , E Riboli , A Winkvist & R Palmqvist (2006) Low folate levels may protect against colorectal cancer. Gut 55, 14611466.

67. KH Bonaa , I Njolstad , PM Ueland , H Schirmer , A Tverdal , T Steigen , H Wang , JE Nordrehaug , E Arnesen & K Rasmussen ; NORVIT Trial Investigators (2006) Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354, 15781588.

68. CM Carlsson (2007) Lowering homocysteine for stroke prevention. Lancet 369, 18411842.

69. X Wang , X Qin , H Demirtas , J Li , G Mao , Y Huo , N Sun , L Liu & X Xu (2007) Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 369, 18761882.

70. J Toole , M Malinow , L Chambless , JD Spence , LC Pettigrew , VJ Howard , EG Sides , CH Wang & M Stampfer (2004) Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) Randomized Controlled Trial. JAMA 291, 565575.

71. JB Mason , A Dickstein , PF Jacques , P Haggarty , J Selhub , G Dallal & IH Rosenberg (2007) A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev 16, 13251329.

74. Z Li , J Gindler , H Wang , RJ Berry , S Li , A Correa , JC Zheng , JD Erickson & Y Wang (2003) Folic acid supplements during early pregnancy and likelihood of multiple births: a population-based cohort study. Lancet 361, 380384.

75. JM Lawrence , ML Watkins , V Chiu , JD Erickson , DB Petitti & YI Kim (2004) Food fortification with folic acid and rate of multiple births, 1994–2000. Birth Defects Res A Clin Mol Teratol 70, 948952.

78. O Henao , C Piyathilake , J Waterbor , E Funkhouser , GL Johanning , DC Heimburger & EE Partridge (2005) Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3. Int J Cancer 113, 991997.

79. S Larsson , E Giovannucci & A Wolk (2007) Folate and risk of breast cancer: a meta-analysis. J Natl Cancer Inst 99, 6476.

80. J Durga , MP van Boxtel , EG Schouten , FJ Kok , J Jolles , MB Katan & P Verhoef (2007) Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 369, 208216.

83. JG Ray , MJ Vermeulen , LJ Langman , SC Boss & DE Cole (2003) Persistence of vitamin B12 insufficiency among elderly women after folic acid food fortification. Clin Biochem 36, 387391.

85. A Liem , GH Reynierse-Buitenwerf , AH Zwinderman , JW Jukema & DJ van Veldhuisen (2003) Secondary prevention with folic acid: effects on clinical outcomes. J Am Coll Cardiol 41, 21052113.

86.The Heart Outcomes Prevention Evaluation Investigators (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 354, 15671577.

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