Food Fortification in Public Health Policy TH Tulchinsky MD MPH Braun SPH 2 Nov 2004

Essential Considerations Public health and medical responsibility Food industry and regulators involved Create demand - enriched foods, behavior changes Monitor compliance and ID rates National council on nutrition - academic and professional organizations and public reps Long term program Regulatory, monitoring and laboratory support

Public Health Nutrition Strategies Food based strategy Socio economic factors Food supply/costs Supplementation for target groups Women and children Elderly Fortification of basic foods Surveillance and monitoring Education Public Professional

18-19th Century Breakthroughs Lind and scurvy 1747 Lemon juice in Royal Navy, 1796 Davy isolates sodium, potassium, calcium, magnesium, sulphur, boron, 1807 Chatin shows iodine prevents goiter, 1850 Takaki and beriberi, Japanese Navy, 1885 Eijkman publishes cause of beriberi, 1897

Vital Amines 1900, nutrition - calories, fats, carbohydrates proteins 1912, Funk defines vital amines Rickets, scurvy, goiter, beriberi common in industrial countries Pellagra “epidemic” in southern US 1914, Goldberger of USPHS investigates pellagra 1922, McCollum and vitamin D in cod liver oil

Key Landmarks Morton’s iodized salt, 1924 Louisiana - mandates vit B fortification of flour, 1928 US federal mandate - enrichment of flour with vitamins B and iron, 1941 UK and colonies same during WWII

Preventing Goiter and Iodine Deficiency Disorders 1917, high % US draftees rejected - goiter 1922-27, goiter rates fall from 39% to 9% by statewide prevention programs 1924, Morton’s Iodized Salt (N America) 1979, Iodization mandatory in Canada 1980s, WHO - universal iodization of salt Many countries achieved iodization

Iodine Fortification of Salt in the U. S Iodine Fortification of Salt in the U.S.: Trend in Goiter Prevalence in Michigan WHO Monograph Series N. 44

Pellagra: The 4 Ds Diarrhea, dermatitis, dementia, death Thought to be of infectious origin Common in prisons, mental institutions, sharecroppers in southern US Curable by dietary change (Goldberger) 1929, niacin found as essential factor 1906-1940, 3 million cases and 100,000 deaths attributed to pellagra

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Rickets 1921, rickets affects 75% of children in New York City schools Cod liver oil commonly used (middle class) 1940s, US fortifies milk with vitamin D dramatically reduces rickets incidence Canada fortifies milk 1940s, then refortifies resulting in increase in rickets in 1960s

Low Cost Solutions to Eliminate Micronutrient Malnutrition Annual Per Capita Cost of Interventions Source: World Bank, 1994

Relative Cost Effectiveness of Micronutrient Interventions Source: UNICEF/UNU/WHO/MI, 1999

Iron Deficiency Commonest MND Affects survival, health and productivity Affects women in age of fertility Affects pregnancy and newborn Affects growth and cognitive development of infants and children Interaction with vitamin C deficiency

Global Burden of Iron Deficiency WHO Region Anemic or Iron Deficient Prevalence of Anemia in Pregnancy Africa America Europe E. Mediterranean S.E. Asia Western Pacific 206 94 27 149 616 1058 52 60 18 50 74 40 Source WHO

Benefits of Preventing Iron Deficiency Benefits to children Improved behavioral and cognitive development Improved child survival (where severe anemia is common) Benefits to adolescents Improved cognitive performance Better iron stores for later pregnancies (females)

Benefits to Pregnant Women and Their Infants Decreased low birth weight and perinatal mortality Decreased maternal mortality and obstetrical complications (where severe anemia is common) Benefits to all Individuals Improved fitness and work capacity Improved cognition Increased immunity Lower morbidity from infectious disease

Trends in Prevalence of Anemia. in Low-income U. S Trends in Prevalence of Anemia* in Low-income U.S. Children, 12-17 Months Old *Hgb <10.3 g/dL Yip et al., JAMA, 1987

Preschool children School age children and adolescents Non-pregnant women Pregnant women Adult men

Prevalence of iron deficiency. by income and race/ethnicity, U. S Prevalence of iron deficiency* by income and race/ethnicity, U.S., 1-4 year olds, 1988-94 *Based on serum ferritin model NHANES III (Ogden et al., 1998)

US Federal Policy USDA extension programs 1921-29, US Maternal and Infancy Act - state health departments employ nutritionists 1930s, relief/commodity distribution 1941, enriched wheat flour with iron, vit B 1941, US establishes RDAs Food stamps, WIC, school lunch programs National nutrition surveys

Canada 1979 National nutrition survey 1971 Geographic, social and ethnic deficiencies Process of consultation 1979 federal regulations, mandatory Vitamin A and D in all milk products Iodine in salt Vitamins B and iron in flour

Epidemiologic Revolution 1960s-1980s Risk factors for chronic disease Health field concept Health for All Declining mortality from stroke and CHD, trauma Advances in drugs and diagnostics Control of infectious diseases Rapid increase in costs of care: health system reform

Nutrition Interactions Iodine Deficiency – psychomotor retardation Iron Def Anemia and infectious diseases Iron promotes growth and development Vitamin A and infectious diseases e.g. measles Vitamin A promotes growth Folic acid prevents birth defects Folic acid with CVD, Alzheimer’s Disease Nutrition and cancer Nutrition and cardiovascular disease Nutrition and diabetes Nutrition in disease management

Folic Acid and NTDs Pre pregnancy folic acid supplements prevent neural tube defects, 1980s Supplements to women in age of fertility achieves <1/3 coverage, 1990s (US) FDA mandates fortification of “enriched” flour, from 1998 Canada and UK also mandate folic acid fortification of flour New paradigm in public health

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Global prevention of all folic acid-preventable spina bifida and anencephaly by 2010. Oakley GP. Community Genet. 2002 Sep;5(1):70-7. Spina bifida and anencephaly are pandemic, affecting 225,000 children a year. Need commitment to global prevention of all folic acid-preventable spina bifida and anencephaly (FA-P SBA) by 2010. Folic acid fortification of centrally processed foods, such as wheat and corn flour, could immediately prevent all of these birth defects for much of the world's population. Fortification programs also help adults by increasing serum folate concentration, eradicating folate deficiency anemia, provide human genome stability and reduce homocysteine serum levels. Probably prevent heart attacks and strokes, and may prevent colon cancer and Alzheimer's disease.

Folic Acid Supplements and Fortification Affect the Risk for Neural Tube Defects, Vascular Disease and Cancer: Evolving Science. Folic acid supplements reduce the risk of NTDs and may be associated with reduced risk for vascular disease and cancer. Observational and controlled intervention studies support public health policies related to folic acid and NTDs. Educational to promote daily intake of FA supplements by women of reproductive age did not increase supplement use. Food fortification appears to be associated with a reduction in neural tube defects in the United States and Canada Potential for FA supplements to reduce the incidence, severity of vascular disease and cancer is focus of major research including intervention studies. Bailey LB et al. J. Nutr. 133:1961S-1968S, 2003.

Food Fortification Cuts Cases of Spina Bifida in Canada Fortification of food with folic acid dramatically reduces the incidence of spina bifida and other NTDs, without masking vitamin B-12 deficiency in elderly people.. Canadian study in Newfoundland, an area with historically high rates of neural tube defects showed 78% reduction after fortification.. In 1998 fortification of white flour, pasta, and cornmeal with folic acid was imposed in Canada to increase the intake of folic acid of all women of childbearing age.. NTD rates fell from 4.36/1000 births before fortification to 0.96 in 1000 births after fortification.   BMJ Oct 2004

American Academy of Pediatrics Committee on Genetics The AAP endorses the US Public Health Service recommendation that all women capable of becoming pregnant consume 400 µg of folic acid daily to prevent neural tube defects (NTDs). Studies show periconceptional folic acid supplementation prevents 50% or more of NTDs e.g. spina bifida, anencephaly. Implementation of these recommendations is essential for the primary prevention of these serious, disabling birth defects. Because fewer than 1 in 3 women consume amount of folic acid recommended by the USPHS, the AAP notes prevention of NTDs depends on an urgent and effective campaign to close this prevention gap. Pediatrics;104, August 1999; 325-7

Seshadri S, Beiser A, Selhub J, et al. NEJM. 346;7:476-483, 2003 Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer's Disease. Elevated plasma homocysteine levels associated with poor cognition, dementia. A total of 1092 subjects without dementia (667 women and 425 men (mean age, 76 years) from the Framingham Study study sample. Examined the relation of the plasma total homocysteine level measured at base line and eight years earlier. Over period of eight years, dementia developed in 111 subjects, including 83 with Alzheimer's disease. Multivariable-adjusted RR of dementia was 1.4 (CI 1.1 to 1.9) for each increase of 1 SD in the homocysteine value at base line or eight years earlier. The RR of Alzheimer's disease was 1.8 (CI-1.3 to 2.5) per increase of 1 SD at base line and 1.6 (CI 1.2- 2.1) per increase of 1 SD eight years before base line. With a plasma homocysteine level greater than 14 µmol per liter, the risk of Alzheimer's disease nearly doubled. Increased plasma homocysteine level is a strong, independent risk factor for the development of dementia and Alzheimer's disease. Seshadri S, Beiser A, Selhub J, et al. NEJM. 346;7:476-483, 2003

Folic Acid and Heart Disease High homocysteine levels associated with excess CHD, birth defects, Alzheimer’s Disease Folic acid reduces high homocysteine Flour fortification effective in raising FA levels in population Clinical trials of folic acid and CHD underway New paradigm in public health nutrition

Osteoporosis Aging of the population Vit D production in skin seasonal Sun varies by season and latitude even in sunny countries Fortification of calcium popularized Vitamin D lacking in raw milk Calcium, vitamin D, fluoride co-factors Fortifying milk products with Vit D needed

Fortification strategies to meet micronutrient needs Food fortification played important role in the nutritional health, well-being of populations in industrial countries. From early 20th C, fortification targeted specific conditions: goitre with iodized salt; rickets with vitamin D-fortified milk; beriberi, pellagra and anaemia with B-vitamins and Fe-enriched cereals. Recently, in the US, risk of pregnancy affected by NTDs with folic acid-fortified cereals. Enormous increase in fortification programs in developing countries, in reducing vitamin A and I deficiencies, but less so with Fe. Food fortification can play an large role in prevention and control of micronutrient malnutrition.. Proc Nutr Soc. 2002 May;61(2):231-41

Problems with Fortification Policy Antagonism to North American initiatives European resistance e.g. EU Nutritionist focus on clinical approach WHO ambivalence/opposition “Green” attitudes Medical attitudes and lack of interest Resistance to “mandatory medication” Individual choice vs. public good Clinical vs. population approaches Manufacturer’s and regulatory agency attitudes

Progress Decreased contamination and food-borne disease Improved food handling methods - refrigeration Improved nutritional value of foods and crops Food fortification Identifying essential micronutrients Food-fortification programs eliminated rickets, goiter, pellagra in the US, Canada Folic acid and other new disease relationships Micronutrients as functional food elements Genetically engineered foods

Folic acid fortification of wheat flour: Chile. Neural tube defects (open spina bifida, anencephaly, and encephalocele) represent the first congenital malformations to be preventable through public health measures such as supplementation and/or food fortification with folic acid. In Chile, starting in January 2000, the Chilean Ministry of Health legislated to add folic acid to wheat flour (2.2 mg/kg) to reduce the risk of NTDs. This policy resulted in an estimated mean additional supply of 427 microg/d in significant increases in serum folate and red cell folate of 3.8 and 2.4-fold, respectively, in women of fertile age, one year after fortification. The impact on the rate of NTDs is presently being studied in all births, both live births and still births, with birth weight >500 g in the city of Santiago. Preliminary results show a reduction of 40% in the rates on NTDs from the pre-fortification period (1999-2000) to post-fortification period (2001-June 2002). Fortification of wheat flour with folic acid in Chile is effective in preventing NTDs in Chile. Nutr Rev. 2004 Jun;62:S44-8;

Changes in NTD prevalence rates after folic acid fortification in South America Several South American countries are fortifying wheat flour with folic acid. Chile started in 2000 to add 2.2 mg/kg, providing 360 mcg daily per capita. Data from 361,374 births occurred in 43 South American hospitals, in five countries, in 1999-2001. Chile, showed decrease of 31% during the 2000-2001. Significance (P < 0.001) reached in the 20th month after fortification started. Am J Med Genet. 2003 Dec 1;123A:123-128

Recent Findings in Israel Berry Committee recommends fortification 1986 Process of implementation slow Anemia rates declining but still high Iodine deficiency – Sack, Mates et Folic acid low, homocysteine levels high, vit B12 levels low (Kark) Voluntary fortification Mandatory fortification of flour, salt and milk products – regulations in progress

DMFT in Europe 040701 Decayed, missing or filled 1 2 3 4 5 6 7 1970 1980 1990 2000 2010 Germany Israel Slovenia United Kingdom 040701 Decayed, missing or filled teeth at age 12 (DMFT-12 index)

Conclusion Nutrition a major public health issue Fortification is one of the key PH inteventions Affects MCH, infectious, non infectious disease High priority – birth defects, IDA, IDD, CHD Fortification has low sex appeal vs. clinical Rx or Px Mandatory vs. voluntary – false dilemma Requires concern, knowledge, conviction, advocacy, persistence and leadership Population health perspective Public health role is to implement successful inteterventions

Referent Agencies World Health Organization UNICEF Centers for Disease Control American Academy of Pediatrics American College Obstetrics and Gynecology US Food and Drug Administration Health Canada March of Dimes World Bank Micronutrient International and other NGOs