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

Abstract Objective To quantify the health and economic outcomes associated with changes in folic acid consumption following the fortification of enriched grain products in the USA. Design Cost-effectiveness analysis. Setting 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. Subjects 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. Results 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. Conclusions 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.

[1]  J. Mosbech,et al.  Morbidity of pernicious anaemia. Incidence, prevalence, and treatment in a Danish county. , 2009, Acta medica Scandinavica.

[2]  Rongwei Fu,et al.  Screening for Colorectal Cancer: A Targeted, Updated Systematic Review for the U.S. Preventive Services Task Force , 2008, Annals of Internal Medicine.

[3]  V. Ganji,et al.  Proportion of individuals with low serum vitamin B-12 concentrations without macrocytosis is higher in the post folic acid fortification period than in the pre folic acid fortification period. , 2007, The American journal of clinical nutrition.

[4]  P. Verhoef,et al.  Folic acid fortification: is masking of vitamin B-12 deficiency what we should really worry about? , 2007, The American journal of clinical nutrition.

[5]  H. Powers Folic acid under scrutiny. , 2007, The British journal of nutrition.

[6]  I. Rosenberg,et al.  A Temporal Association between Folic Acid Fortification and an Increase in Colorectal Cancer Rates May Be Illuminating Important Biological Principles: A Hypothesis , 2007, Cancer Epidemiology Biomarkers & Prevention.

[7]  Elizabeth L. Barry,et al.  Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. , 2007, JAMA.

[8]  C. Carlsson Lowering homocysteine for stroke prevention , 2007, The Lancet.

[9]  Xiping Xu,et al.  Efficacy of folic acid supplementation in stroke prevention: a meta-analysis , 2007, The Lancet.

[10]  Petra Verhoef,et al.  Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial , 2007, The Lancet.

[11]  S. Larsson,et al.  Folate and risk of breast cancer: a meta-analysis. , 2007, Journal of the National Cancer Institute.

[12]  K. Reynolds,et al.  Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. , 2006, JAMA.

[13]  D. Wald,et al.  Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence , 2006, BMJ : British Medical Journal.

[14]  W. Willett,et al.  Population-level changes in folate intake by age, gender, and race/ethnicity after folic acid fortification. , 2006, American journal of public health.

[15]  J. Blacher,et al.  Homocysteine lowering with folic acid and B vitamins in vascular disease, The Heart Outcomes Prevention Evaluation (HOPE) 2 investigators , 2006 .

[16]  H. Boeing,et al.  Dietary intake of folate equivalents and risk of myocardial infarction in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam study , 2006, Public Health Nutrition.

[17]  J. Stempak,et al.  Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. , 2006, Carcinogenesis.

[18]  E. Riboli,et al.  Low folate levels may protect against colorectal cancer , 2006, Gut.

[19]  Per Magne Ueland,et al.  Homocysteine lowering and cardiovascular events after acute myocardial infarction. , 2006, The New England journal of medicine.

[20]  P. Wolf,et al.  Heart disease and stroke statistics--2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. , 2006, Circulation.

[21]  P. Romano,et al.  Reevaluating the benefits of folic acid fortification in the United States: economic analysis, regulation, and public health. , 2005, American journal of public health.

[22]  L. Edmonds,et al.  Decline in the Prevalence of Spina Bifida and Anencephaly by Race/Ethnicity: 1995–2002 , 2005, Pediatrics.

[23]  E. Funkhouser,et al.  Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3 , 2005, International journal of cancer.

[24]  D. Petitti,et al.  Food fortification with folic acid and rate of multiple births, 1994-2000. , 2004, Birth defects research. Part A, Clinical and molecular teratology.

[25]  Young-In Kim Will mandatory folic acid fortification prevent or promote cancer? , 2004, The American journal of clinical nutrition.

[26]  A. Correa,et al.  Trends in twinning rates in metropolitan Atlanta before and after folic acid fortification. , 2004, The Journal of reproductive medicine.

[27]  E. Arias United States Life Tables, 2001. , 2004, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[28]  L. Chambless,et al.  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. , 2004, JAMA.

[29]  B. Hamilton,et al.  Revised birth and fertility rates for the 1990s and new rates for Hispanic populations, 2000 and 2001: United States. , 2003, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[30]  D. Cole,et al.  Persistence of vitamin B12 insufficiency among elderly women after folic acid food fortification. , 2003, Clinical biochemistry.

[31]  A. Zwinderman,et al.  Secondary prevention with folic acid: effects on clinical outcomes. , 2003, Journal of the American College of Cardiology.

[32]  J. Mills,et al.  Low vitamin B-12 concentrations in patients without anemia: the effect of folic acid fortification of grain. , 2003, The American journal of clinical nutrition.

[33]  A. Correa,et al.  Folic acid supplements during early pregnancy and likelihood of multiple births: a population-based cohort study , 2003, The Lancet.

[34]  G. Shaw,et al.  Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United States , 2003 .

[35]  T. J. Mathews,et al.  Spina bifida and anencephaly prevalence--United States, 1991-2001. , 2002, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[36]  Michael Pignone,et al.  Cost-Effectiveness Analyses of Colorectal Cancer Screening , 2002, Annals of Internal Medicine.

[37]  G. Shaw,et al.  Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United States. , 2002, Teratology.

[38]  G. Stone,et al.  Cost-Effectiveness of Coronary Stenting in Acute Myocardial Infarction: Results From the Stent Primary Angioplasty in Myocardial Infarction (Stent-PAMI) Trial , 2001, Circulation.

[39]  M. Law,et al.  Quantifying the effect of folic acid , 2001, The Lancet.

[40]  R. Hayward,et al.  Which colon cancer screening test? A comparison of costs, effectiveness, and compliance. , 2001, The American journal of medicine.

[41]  L. Goldman,et al.  Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease: effect of grain fortification and beyond. , 2001, JAMA.

[42]  Graham A. Colditz,et al.  Cost-effectiveness of screening for colorectal cancer in the general population. , 2000, JAMA.

[43]  J. Mitchell,et al.  A DECISION MODEL AND COST-EFFECTIVENESS ANALYSIS OF COLORECTAL CANCER SCREENING AND SURVEILLANCE GUIDELINES FOR AVERAGE-RISK ADULTS , 2000, International Journal of Technology Assessment in Health Care.

[44]  Ann M Holmes,et al.  Cost-utility of one-time colonoscopic screening for colorectal cancer at various ages , 2000, American Journal of Gastroenterology.

[45]  J D Habbema,et al.  Endoscopic colorectal cancer screening: a cost-saving analysis. , 2000, Journal of the National Cancer Institute.

[46]  R. Dittus,et al.  Utility valuations for outcome states of colorectal cancer , 1999, American Journal of Gastroenterology.

[47]  K. Kuntz,et al.  Cost-effectiveness of diagnostic strategies for patients with chest pain. , 1999, Annals of internal medicine.

[48]  J. R. Bentley,et al.  American College of Preventive Medicine public policy statement. Folic acid fortification of grain products in the U.S. to prevent neural tube defects. , 1999, American journal of preventive medicine.

[49]  F. Speizer,et al.  Multivitamin Use, Folate, and Colon Cancer in Women in the Nurses' Health Study , 1998, Annals of Internal Medicine.

[50]  M. Stanton,et al.  Homocysteine and cardiovascular disease , 2011 .

[51]  J. Manson,et al.  Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. , 1998, JAMA.

[52]  S. Daly,et al.  Minimum effective dose of folic acid for food fortification to prevent neural-tube defects , 1997, The Lancet.

[53]  R. Baumgartner,et al.  Folate nutrition and older adults: challenges and opportunities. , 1997, Journal of the American Dietetic Association.

[54]  P. Wilson,et al.  Folic acid fortification of the food supply. Potential benefits and risks for the elderly population. , 1996, JAMA.

[55]  R. Carmel Prevalence of undiagnosed pernicious anemia in the elderly. , 1996, Archives of internal medicine.

[56]  D. Weir,et al.  Folate levels and neural tube defects. Implications for prevention. , 1995, JAMA.

[57]  P. Romano,et al.  Folic acid fortification of grain: an economic analysis. , 1995, American journal of public health.

[58]  C. Dickinson Does folic acid harm people with vitamin B12 deficiency? , 1995, QJM : monthly journal of the Association of Physicians.

[59]  D. Pryor,et al.  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. , 1995, JAMA.

[60]  Harold C. Sox,et al.  Variation in Patient Utilities for Outcomes of the Management of Chronic Stable Angina: Implications for Clinical Practice Guidelines , 1995 .

[61]  S. Shapiro,et al.  Periconceptional folic acid exposure and risk of occurrent neural tube defects. , 1993, JAMA.

[62]  A. Czeizel,et al.  Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. , 1992, The New England journal of medicine.

[63]  M. Gnant,et al.  Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study , 1991, The Lancet.

[64]  F. Sonnenberg,et al.  Myocardial revascularization for chronic stable angina. Analysis of the role of percutaneous transluminal coronary angioplasty based on data available in 1989. , 1990, Annals of internal medicine.

[65]  R M Kaplan,et al.  A general health policy model: update and applications. , 1988, Health services research.

[66]  K. Borch,et al.  Prevalence and incidence of pernicious anemia. An evaluation for gastric screening. , 1984, Scandinavian journal of gastroenterology.

[67]  E. F. Beach,et al.  Economic Models , 1957 .

[68]  I. Rosenberg,et al.  Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. , 2007, The American journal of clinical nutrition.

[69]  Folate status in women of childbearing age, by race/ethnicity--United States, 1999-2000, 2001-2002, and 2003-2004. , 2007, MMWR. Morbidity and mortality weekly report.

[70]  A. A. Liakishev [Homocysteine lowering with folic acid and B vitamins in vascular disease]. , 2006, Kardiologiia.

[71]  E. Feuer,et al.  SEER Cancer Statistics Review, 1975-2003, National Cancer Institute. Bethesda, MD, , 2006 .

[72]  Michael Pignone,et al.  Workshop Agenda: Economic Models of Colorectal Cancer Screening in Average-Risk Adults , 2005 .

[73]  Spina bifida and anencephaly before and after folic acid mandate--United States, 1995-1996 and 1999-2000. , 2004, MMWR. Morbidity and mortality weekly report.

[74]  J. Gerberding,et al.  Folate status in women of childbearing age, by race/ethnicity--United States, 1999-2000. , 2002, MMWR. Morbidity and mortality weekly report.

[75]  Folate status in women of childbearing age--United States, 1999. , 2000, MMWR. Morbidity and mortality weekly report.

[76]  Folic Acid Knowledge and use of folic acid by women of childbearing age--United States, 1995 and 1998. , 1999, MMWR. Morbidity and mortality weekly report.

[77]  Folic Acid Knowledge and use of folic acid by women of childbearing age--United States, 1997. , 1997, MMWR. Morbidity and mortality weekly report.

[78]  A. Czeizel,et al.  The higher rate of multiple births after periconceptional multivitamin supplementation: an analysis of causes. , 1994, Acta geneticae medicae et gemellologiae.

[79]  R Levine,et al.  Prevention and early detection of colorectal cancer. , 1992, American family physician.

[80]  K. Anderson,et al.  Cardiovascular disease risk profiles. , 1991, American heart journal.

[81]  Rascon [The National Cancer Institute]. , 1953, Boletin cultural e informativo - Consejo General de Colegios Medicos de Espana.

[82]  D. Shalala,et al.  Department of Health and Human Services Food and Drug Administration Food Standards: Amendment of Standards of Identity for Enriched Grain Products to Require Addition of Folic Acid , 2022 .