Folic Acid in the Prevention of Birth Defects


>>>GOOD MORNING, EVERYBODY. WELCOME TO THE PUBLIC HEALTH GRAND ROUNDS AT CDC. I WOULD LIKE TO EXTEND A WELCOME NOT ONLY TO THOSE OF YOU JOINING US IN THE AUDITORIUM WHICH IS A MINORITY, BUT ALL OF THOSE WATCHING US ON IPTV AND IN VISIONLAND AND THOSE OF US ACCESSING THIS SESSION THROUGH OUR INTERNET. SINCE THESE EVENTS ARE — AS DR. FRIEDENS SAYS THEMED FROM MEANINGFUL SCIENCE TO IMPACTFUL PRACTICE I’M SURE YOU WOULD LIKE EVIDENCE FROM MY WORDS SAYING LAST TIME WE HAD THE SESSION THERE WERE 4,404 EXTERNAL VIEWERS. FOR A LOT OF PEOPLE SPEAKING THIS IS POSSIBLY THE BIGGEST AUDIENCE THEY HAVE SPOKEN TO. AND HERE IS JUST ONE OF THE PHOTOS WE HAVE RECEIVED FROM THE AUDIENCES WATCHING THE GRAND ROUNDS ON THE WHITE HOUSE LAWN. [ LAUGHTER ] >>I WOULD LIKE TO REMIND YOU THAT WE ARE ELIGIBLE FOR CONTINUING EDUCATION CREDITS STARTING LAST MONTH. ANY INFORMATION YOU NEED, YOU CAN FIND AT THE WEB. I’M ALSO PLEASED TO SAY THAT WE CONTINUED TO COORDINATE INFORMATION PRESENTED AT THESE SESSIONS WITH THAT IN OUR SCIENTIFIC CLIPS. I WOULD LIKE TO THANK DR. BARRY FOR SELECTING THE ARTICLES FOR THIS ISSUE. FINALLY, JUST TO LET YOU KNOW WHAT’S COMING UP THESE ARE TOPICS APPROVED AND I HAVE BEEN WORKING WITH THE E COLLEAGUES ON THAT INFORMATION. WITH THAT, I WILL TURN IT TO OUR DIRECTOR, DR. FRIEDENS, TO SAY A FEW WORDS. >>WE HAVE A FULL AND INTERESTING AND EXCITING SESSION TODAY. I DON’T WANT TO TAKE UP MUCH TIME. I WANT TO THANK THE CONTRIBUTORS AND EVERYONE WHO HAS WORKED ON THIS. 300,000 CHILDREN WILL BE BORN WITH A NEURAL TUBE DEFECT THIS YEAR AROUND THE WORLD. ADDRESSING NEURAL TUBE DEFECTS IS ONE OF THE REAL SUCCESSES OF PUBLIC HEALTH AND THE IMPACT PYRAMID THAT’S BEEN SHOWN BEFORE SHOWS FORTIFICATION OF FOODS IN THAT SECOND TO BOTTOM ROW WHERE A MAJOR IMPACT CAN BE MADE BY CHANGING THE CONTEXT OF DEFAULT DECISIONS ARE HEALTHIER. THAT’S DONE GENERALLY THROUGH REGULATION. THE BENEFITS OF FOLIC ACID HAVE BEEN CONFIRMED THROUGH RIGOROUS RESEARCH AND AS YOU WILL HEAR, THIS IS A PUBLIC HEALTH SUCCESS STORY WITH A PARTNERSHIP BETWEEN SCIENCE, CDC, FDA, AND THE INDUSTRY. BUT THERE ARE CONTINUING CHALLENGES BOTH IN THIS COUNTRY AND ESPECIALLY ABROAD AND SUBSTANTIAL DISPARITY IN THIS COUNTRY. SO THE RESPONSE TO THAT IS GOING TO REQUIRE THAT SAME PARTNERSHIP THAT’S LED TO THE PROGRESS SO FAR. SCIENCE, CDC, FDA AND INDUSTRY. WE ARE DELIGHTED TO HAVE THIS SESSION TODAY TO EXPLORE THAT FURTHER. THANK YOU. >>GOOD MORNING, EVERYONE. I’M JOE MOLINARES, THE PREVENTION AND RESEARCH TEAM ON THE NATIONAL CENTER OF BIRTH DEFECTS AND DEVELOPMENTAL DISABILITIES. TODAY I AM GOING TO START WITH AN OVERVIEW OF NEURAL TUBE DEFECTS AND FOLIC ACID. THEN DR. BILL DEETS WILL PROVIDE STRATEGIES TO REDUCE THE INCIDENCE WORLDWIDE. DR. JOHNSTON WILL TALK ABOUT THE POTENTIAL ADVERSE EFFECTS OF FOLIC ACID AND DR. JESSICA LAYTON WILL TALK ABOUT FORTIFICATION OF CORN MATZA FLOUR. FOR MY PRESENTATION TODAY, I WILL START BY DESCRIBING NEURAL TUBE DEFECTS WHICH I WILL CALL NTDs IN MOST OF THE PRESENTATION. I WILL TALK ABOUT THE EVIDENCE BASE AND EFFICACY OF FOLIC ACID, STRATEGIES TO ACHIEVE LEVELS, IMPACTS OF FOLIC ACID TO REDUCE NTDs IN THE UNITED STATES AND WILL CLOSE BY FOCUSING ON THE CHALLENGES. I’LL START BY DESCRIBING NTDs. SPINA BIFIDA AND ANOCEPHOLY ARE THE MOST COMMON KINDS IF THE NEURAL TUBE FAILS TO CLOSE. ANOCEPHOLY IS WHEN THE — TO THE BRAIN DOESN’T CLOSE. THE BABY WILL DIE SHORTLY AFTER BIRTH. IN MOST CASES OF SPINA BIFIDA THERE IS AN OPENING IN THE BACKBONE AND THE SKIN AROUND IT SO THE SPINAL CORD STICKS OUT UH THROUGH THE BABY’S BACK. DAMAGE TO THE CORD MIGHT VARY. IN MILD CASES THERE MAY BE LOSS OF SENSATION OR MOVEMENT, BUT IN SEVERE CASES THERE IS LOSS OF MOBILITY AND VARYING DEGREES OF LOSS OF BOWEL AND BLADDER CONTROL. SPINA BIFIDA OCCURS ABOUT TWICE AS A OFTEN. NTDs DEVELOP IN THE FIRST MONTH AFTER CONCEPTION, BEFORE MOST WOMEN KNOW THEY ARE PREGNANT. BECAUSE MORE THAN 50% OF WOMEN DO NOT PLAN A PREGNANCY, CONSUMING FOLIC ACID DAILY IS CRITICAL FOR PREVENTION OF SERIOUS BIRTH DEFECTS. STUDIES HAVE SHOWN 50 TO 70% OF NTDs ARE PREVENTABLE BY THE USE OF FOLIC ACID. TO PREVENT THEM IT’S RECOMMENDED WOMEN CAPABLE OF BECOMING PREGNANT NEED TO CONSUME 400 MICRO GRAIM GRAMS DAILY STARTING PRIOR TO CONCEPTION AND THROUGH THE FIRST TRIMESTER. SINCE 1995 THE NATIONAL BIRTH DEFECT PREVENTION CENTER HAS BEEN CONDUCTING RESEARCH ON 25 SURVEILLANCE SYSTEMS. THE RESULTS SHOWED IN THE UNITED STATES BEFORE FORT CAN I TAGS OF GRAIN PRODUCTS ABOUT 4,000 PREGNANCIES UH-OH CUREDER EACH YEAR WITH A NTD. AFTER FORTIFICATION THE NUMBER DECREASED TO 3,000 AFFECTED PREGNANCIES. SINCE FORTIFICATION BEGAN 12 YEARS AGO MORE THAN A 12,000 BABIES HAVE BEEN BORN WITHOUT NTDs. WORLDWIDE THERE ARE AN ESTIMATED 300 TO 350,000 NTDs OCCURRING EVERY YEAR. THIS CHART SHOWS THE DISTRIBUTION AMONG TEN COUNTRIES WITH THE GREATEST NUMBER OF NTDs. THE CHALLENGE OF PREVENTABLE NTDs IS GREAT. SO WHAT’S THE SCIENTIFIC EVIDENCE? WHAT’S THE SCIENTIFIC EVIDENCE FOR PREVENTION OF NTDs? FIRST, LET ME DEFINE TERMS. FOLATE IS A GENERIC TERM FOR B-9. ONE FORM IS FOUND IN FOODS LIKE BEEF LIVER, FRUITS, VEGETABLES, BEANS AND WHOLE GRAINS. FOLIC ACID IS THE SYNTHETIC KIND FOUND IN FORTIFIES FOODS. THE ACID IS MORE AVAILABLE. SO MORE THE PURPOSES OF BIOAVAILABILITY 400 MICRO GRAMS CAN BE EQUATED TO 800 MICRO GRAMS OF FOOD FOLATE. EVIDENCE FOR THE REDUCTION OF THE RISK OF NTDs WITH FOLIC ACID HAS BEEN DEMONSTRATED IN 20 YEARS OF ON VARIABLE, NONRANDOMIZED PREVENTION AND NONRANDOMIZED TRIALS. THEY HAVE SHOWN REDUCTIONS IN THE RISK OF NTDs RANGING FROM 59% TO 100%. A POPULATION-BASED COMMUNITY INTERVENTION THAT WAS PUBLISHED IN 19 T 9 FROM CHINA HELPED TO VALIDATE THAT DAILY USE OF 400 MICRO GRAMS OF FOLIC ACID ALONE WOULD PREVENT NTDs. IN ADDITION IT SHOWED THAT IN THE TWO REGIONS STUDIED — THE NORTH WHICH HAD HIGH PREVALENCE OF NTDs, ABOUT 48 PER 10,000 BIRTHS. IN CONTRAST IN THE SOUTH, THE PREVALENCE WAS MORE LIKE RATES IN DEVELOPED COUNTRIES — U.S., CANADA OR OTHER EUROPEAN COUNTRIES. THOUGH THE INITIAL PREVALENCE OF NTDs WERE DIFFERENT IN TRIAGES TAKING 400 MICRO GRAMS OF FOLIC ACID SHOWED AN EFFECT ON THE FINAL PREVALENCE BETWEEN SIX AND SEVEN PER 10,000 AS INDICATED BY THE RED LINE. NEXT ARE STRATEGIES TO ACHIEVE FOLATE LEVELS IN WOMEN OF CHILD BEARING AGE. THERE ARE THREE APPROACHES TO INCREASING INTAKE OF FOLATE AND FOLIC ACID. THE FIRST IS TO IMPROVE DIETARY HABITS. THE SECOND IS TO TAKE A DAILY FOLIC ACID SUPPLEMENT. THE THIRD APPROACH IS TO FORTIFY FOODS WITH FOLIC ACID. SO HOW COULD A PERSON POSSIBLY GET ENOUGH TO TATE IN THEIR DIET? ONE MIGHT FEAST ON FOUR SLICES OF BEEF LIVER OR 44 AND A HALF MEDIUM RIPE TOMATOES, 17 AND A HALF CUPS OF CONCENTRATED ORANGE JUICE. HARDLY AN EASY OBJECTIVE FOR MOST PEOPLE. IN 1996, IRISH RESEARCHERS CARRIED OUT A STUDY TO ASSESS THE EFFECTIVENESS OF THE THREE FOOD SOURCES AND FOUND THAT COMPREHENSIVE DIETARY ADVICE FOR DELIVERY OF FOLATE RICH FOODS INCREASED THE RED CELL LEVEL LITTLE. ABOUT 16 OR 11% RESPECTIVELY. ON THE OTHER HAND, CONSUMPTION OF SUPPLEMENTS AND FOODS FORTIFIED WITH FOLIC ACID RESULTED IN SUBSTANTIAL INCREASES IN BLOOD FOLATE CONCENTRATION. 40 AND 52% RESPECTIVELY. THIS DEMONSTRATES FOR THE BODY TO ABSORB SUFFICIENT AMOUNTS, SUPPLEMENTS, FORTIFIED FOODS OR BOTH ARE NECESSARY. WHEN THE 1992 PUBLIC HEALTH SERVICE RECOMMENDATION LAID OUT OPTIONS FOR ACCESSING FOLATE — I’M SORRY. WHILE THE RECOMMENDATION LAID OUT OPTIONS FOR ACCESSING FOLATE, IT IS THE 1996 FDA REGULATION THAT HAS MADE FOLIC ACID AVAILABLE TO THE WIDEST POPULATION. THIS WAS RECOGNIZED IN 1998 BY THE INSTITUTE OF MEDICINE WHICH RECOMMENDED THAT WOMEN CAPABLE OF BECOMING PREGNANT SHOULD TAKE 400 MICRO GRAMS OF FOLIC ACID DAILY FROM FORTIFIED FOODS, SUPPLEMENTS OR BOTH IN ADDITION TO CONSUMING FOOD FOLATE FROM A VARIED DIET. WHAT’S THE IMPACT OF FOLIC ACID USE? THESE DATA SHOW THE PERCENT OF PEOPLE WITH SERUM FOLATE GREATER THAN 20 NANOGRAMS BEFORE FORTIFICATION. SERUM LEVELS COULDN’T BE ASSESSED HIGHER BECAUSE THIS WAS THE MAX NUMB LEVEL IN THE LABORATORY. IN 1994 TO 1996 APPROXIMATELY 25% OF SERUM FOLATE CONCENTRATIONS WERE GREATER THAN 20 NANO GRAMS PER MING L. 1996 TO 1997 MANUFACTURERS HAD THE OPTION TO ADD FOLIC ACID TO ENRICHED FOOD. MANUFACTURERS PROVIDED A THREE-YEAR TRANSITION PERIOD. FINALLY, AFTER 1998 WITH MANDATORY FORTIFICATION IMPLEMENTED ALMOST 80% OF SERUM FOLATE SYMBOLS WERE GREATER THAN 20 NANOGRAMS. THIS SHOWED THE EFFECTIVENESS OF RAISING THE CONCENTRATION IN THE POPULATION. THERE WAS OTHER DATA THAT SHOWED CONSUMPTION OF FOLIC ACID THROUGH SUPPLEMENTS HAD REMAINED PRETTY MUCH THE SAME. THAT’S WHY WE CAN ATTRIBUTE THE INCREASE TO FORTIFIED FOODS AS WELL AS SUPPLEMENTS. LET’S TAKE A LOOK AT THE TREND OF NTD RATES. THE SURVEILLANCE PROGRAMS COVER ABOUT TWO MILLION BIRTHS OF THE FOUR MILLION THAT OCCUR ANNUALLY IN THE UNITED STATES. NTD PREVALENCE SHOWED A SIGNIFICANT 26% DECLINE FROM BEFORE FORTIFICATION TO IMMEDIATELY AFTER FORTIFICATION. SINCE 2001 NTD PREVALENCE HAS DECLINED BY AN ADDITIONAL 10%. SO NTD PREVALENCE DECLINED SUBSTANTIALLY ALLOWING US TO ASSESS THE ECONOMIC IMPACT IN THE U.S. THE COST OF FORTIFICATION IS $3 MILLION PER YEAR. TOTAL MEDICAL DIRECT COSTS WERE CONSERVATIVELY ESTIMATED AT $145 MILLION PER YEAR. SO FOR EVERY DOLLAR INVESTED, MORE THAN $45 IN MEDICAL COSTS WERE AVERTED. TODAY WE CALCULATE THE LIFETIME MEDICAL COSTS FOR A BABY BORN WITH SPINA BIFIDA IS CLOSE TO $400,000. THERE ARE SIGNIFICANT COST SAVINGS IN THE U.S. AND IN OTHER COUNTRIES AROUND THE WORLD. NEXT, TURNING TO EXISTING CHALLENGES, LET’S TALK ABOUT TARGETING HIGH RISK POPULATIONS AND GLOBAL FORTIICATION EFFORTS. THERE ARE OTHER RISK FACTORS THAT ARE ASSOCIATED WITH NTDs. I’M ONLY GOING TO SPEND TIME TALKING ABOUT ONE, RACE ETHNICITY, AS THAT INCLUDES A VERY IMPORTANT HIGH RISK GROUP, HISPANICS. THEY HAD THE HIGHEST RATES IN THE U.S. A 45% OVERALL DECLINE AFTER FORTIFICATION WAS OBSERVED IN THE THREE MAJOR RACE ETHNIC GROUPS IN THE U.S. HISPANICS BEGAN WITH THE HIGHEST PREVALENCE OF NTDs AND THE TREND HAS CONTINUED. BECAUSE OF THE OBSERVATION WE FOCUSED OUR EFFORTS ON BETTER UNDERSTANDING AND REDUCING THE HIGHER PREVALENCE AMONG HISPANICS. IN ADDITION TO TARGETED EDUCATIONAL CAMPAIGNS, ANOTHER APPROACH WE EXPLORED IS TO FORTIFY FOODS UNIQUE TO HISPANIC CULTURE AND IN THE U.S. THAT’S MOSTLY MEXICAN-AMERICANS, INCLUDING TORTILLAS AND OTHER FOODS MADE OF CORN MATZA FLOUR. IN JULY 2006 THE POSSIBILITY OF FORTIFYING THE FLOUR WAS DISCUSSED ALL THE THE NATIONAL COUNCIL OF LERAZA. AT THAT TIME, THE LEADING MANUFACTURER OF THE PRODUCTS IN THE U.S. HAD ANNOUNCED THE INITIATION OF RESEARCH AND PRODUCT TESTING WITH THE GOAL OF FORTIFYING CORN PRODUCTS WITH FOLIC ACID. THE NATIONAL COUNCIL WITH SEVERAL PARTNERS PROPOSED TO EXAMINE MAKING AVAILABLE FOLIC ACID FORTIFIED CORN MATZA FLOUR TO PREVENT NTDs IN HISPANICS. CDC PROVIDED ASSISTANCE AND TO MODEL THE USE OF CORN MATZA FLOUR AS A VEHICLE TO ADD FOLIC ACID TO THE DIET. FROM THIS WE LEARNED 21% OF MEXICAN-AMERICAN WOMEN CONSUMED FOLIC ACID SUPPLEMENTS IN CONTRAST TO 37% OF WHITE NONHISPANIC WOMEN. WHILE 60% OF MEXICAN-AMERICAN WOMEN CONSUMED THE CORNFLOWER. SO CDC MODELS WHETHER ADDING FOLIC ACID TO CORN MATZA FLOUR COULD INCREASE THE INTAKE WITHOUT SUBSTANTIALLY INCREASING IT WITHIN OTHER GROUPS. WITH THE FORTIFICATION FOR MEXICAN-AMERICANS THE ACTUAL INTAKE OF FOLIC ACID COULD INCREASE 20% WHILE AT THE SAME TIME THE INCREASE FOR OTHER GROUPS WOULD BE ONLY 4 TO 5%. THERE WOULD BE AN ESTIMATED 7% MORE MEXICAN-AMERICAN WOMEN TO THOSE ALREADY CONSUMING 400 MICRO GRAMS OF FOLIC ACID. BY ADDING FOLIC ACID TO CORN MA STRKS ZA FLOUR THE NUMBER OF BABIES BORN WITHOUT NTDs COULD BE INCREASED 50%. THE RATES GLOBALLY, DR. DEETS WILL HAVE A DETAILED ACCOUNT OF THE GLOBAL FORTIFICATION IN HIS PRESENTATION. I WOULD LIKE TO SHOW YOU THE EXPERIENCE OF FOUR COUNTRIES THAT DEMONSTRATE NUMBERS SIMILAR TO THE UNITED STATES. HERE IS THE DATA I TALKED ABOUT. 37% REDUCTION IN THE U.S. HERE ARE THE FOUR ADDITIONAL COUNTRIES — CANADA, COSTA RICA, CHILE AND SOUTH AFRICA. THEY SHOWED MARKED DECLINES IN NTDs. THE YEAR IN WHICH THE FORTIFICATION TAKES PLACE COUNTRY TO COUNTRY IS DIFFERENT AND THE NUMBER OF YEARS OF DATA AFTER FORTIFICATION IS ALSO DIFFERENT. SO IN SUMMARY, NTDs ARE LIFE-THREATENING AND CAUSE LIFELONG DISABILITIES. 50 TO 70% OF NTDs CAN BE PREVENTED WITH FOLIC ACID DAILY. FORTIFICATION OF FOODS AND FLOUR WITH FOLIC ACID IS FEASIBLE, ECONOMICAL, SAFE AND EFFECTIVE PUBLIC HEALTH POLICY TO PROVIDE FOLIC ACID AND PREVENT NTDs WORLDWIDE. TODAY, BECAUSE OF EXCELLENT MEDICAL CARE, EDUCATIONAL OPPORTUNITIES AND SUPPORTIVE SERVICES, BABIES BORN WITH SPINA BIFIDA HAVE THE OPPORTUNITIES TO LEAD FULL LIVES. THESE CHILDREN AND ADULTS STILL ENCOUNTER DIFFICULTY IN THEIR DAILY LIVES. INCREASING THE INTAKE OF FOLIC ACID KEPT THOUSANDS OF PEOPLE FROM GOING THROUGH THESE EXPERIENCES. HOW WILL WE KNOW WHEN WE HAVE ELIMINATED ALL FOLIC ACID PREVENTABLE NEURAL TUBE DEFECTS? IS IT WHEN WOMEN REACH A PRESET BLOOD CONCENTRATION LEVEL, WHEN NTD RATES ARE AT A CERTAIN LEVEL OR WHEN WE UNDERSTAND THE BIOLOGY OF NTD PREVENTION? IN CONCLUSION, AGGRESSIVE EFFORTS WILL BE NECESSARY TO IMPLEMENT GLOBAL FORTIFICATION OF FOOD STAPLES LIKE THE ERADICATION EFFORTS THAT RED TO THE DISAPPEARANCE OF SMALLPOX WORLDWIDE AND POLIO. THIS IS VERY POSSIBLE. WE NEED TO TURN THIS GREAT PUBLIC HEALTH OPPORTUNITY, ONE NOW WELL ESTABLISHED BY SOUND SCIENCE AND PUBLIC HEALTH POLICY, INTO A REALITY. TO BE SUCCESSFUL, SEVERAL EFFORTS ARE NEEDED. WE NEED TO STRENGTHEN GLOBAL PARTNERSHIPS TO SUPPORT MANDATORY FOLIC ACID FORTIFICATION, CREATE A TECHNICAL RESOURCE CENTER TO ASSIST COUNTRIES IN THEIR MONITORING AND EVALUATION OF PREVENTION PROGRAMS, PROVIDE STRONG COMMUNICATION PROGRAMS TO PROMOTE, ESTABLISH AND SUSTAIN MANDATORY FORTIFICATION AND FINALLY WE NEED TO EXPAND THE SCIENCE BASE FOR GLOBAL MANDATORY FORTIFICATION TO INCLUDE — AND ESPECIALLY TO INCLUDE EVALUATIONS RELATED TO ADVERSE EFFECTS OF FOLIC ACID. THANK YOU. I WILL NOW INTRODUCE DR. DEETS FOR A PRESENTATION ON GLOBAL FOLIC ACID FORTIFICATION. >>GOOD MORNING. I’M BILL DEETS. I PLAN TO COVER THE BROADER RATIONALE FOR THE FORTIFICATION TO TALK ABOUT MICRO NUTRIENT MALNUTRITION. TO TALK ABOUT FLOUR FORTIFICATION, THE IMPACT THAT THE UNIQUE PARTNERSHIP HAS HAD ON WORLDWIDE FORTIFICATION AND THE CHALLENGE THAT IS REMAIN. WORLDWIDE MICRO NUTRIENT DEFICIENCIES ARE ASSOCIATED WITH A BURDEN OF DISEASE. VITAMIN A AND ZINC DEFICIENCY AND FOLIC ACID DEFICIENCY AFFECT MILLIONS OF CHILDREN WORLDWIDE. AS TOM SAID, 300,000 CHILDREN A YEAR ARE BORN WITH NEURAL TUBE DEFECTS ASSOCIATED WITH FOLIC ACID DEFICIENCY. ONLY ABOUT 10% OF ALL POTENTIAL CASES OF ANNUAL NEURAL TUBE DEFECTS ARE CURRENTLY PREVENTED BY FORTIFORTIFICATION. WITH ADEQUATE LEVELS IN WHEAT FLOUR AND OTHER STAPLES WE BELIEVE WE CAN REDUCE THE INCIDENCE WORLDWIDE BY ANOTHER 150,000 CASES PER YEAR. IN 2004 AND 2008 A NUMBER OF THE WORLD’S TOP ECONOMISTS INCLUDING FIVE NOBEL PRIZE WINNERS MET IN COPENHAGEN AND AGREED THAT NUTRITION INTERVENTIONS ARE AMONG THE MOST COST EFFECTIVE WAYS TO ADDRESS GLOBAL DISEASE CHALLENGES. THE PANEL CONCLUDED THAT BATTLING MALNUTRITION IN CHILDREN WITH VITAMIN A AND ZINC WAS THE MOST IMPORTANT AND COST EFFECTIVE STRATEGY. FORTIFICATION IN FLOUR WITH IRON TIED WITH SALT IONIZATION. 30% OF 400 MILLION TONS OF WHEAT FLOUR MILLED FOR HUMAN CONSUMPTION IS CURRENTLY FORLT IDENTIFIED WITH EITHER IRON OR FOLIC ACID. FLOUR MILLING MAKES FORTIFICATION AN EASY AND SUSTAINABLE WAY TO PROVIDE MICRO NUTRIENTS. FORTIFICATION WITH IRON AND FOLIC ACID IS COST EFFECTIVE. THE MOST COSTLY PART OF THIS IS THE FEEDER WHICH ADDS THE FOLIC ACID AND IRON TO THE FLOUR. THE COST OF PREMIX PER METRIC TON DEPENDS ON THE FORTIFICANT. IN THIS CASE IT’S ABOUT A DOLLAR A TON TO ENRICH A TON OF FLOUR WITH FOLIC ACID AND IRON. BECAUSE QUALITY ASSURANCE MEASURES CAN ASSESS THE EFFECTIVENESS OF IRON FORTIFICATION AND BECAUSE NO QUALITY ASSURANCE MEASURE IS AVAILABLE FOR FOLIC ACID, COMBINED FORTIFICATION PERMITS THE MEASUREMENT OF THE EFFECTIVENESS OF THE FORTIFICATION PROCESS. THERE ARE TWO CONCERNS. FIRST, MILLING PROFITS ARE MARGINAL. APPROXIMATELY $1 PER METRIC TON, THE COST OF THE PREMIX. THEREFORE A MILLER WHO CHOOSES TO FORTIFY VOLUNTARILY IS AT A COMPETITIVE DISADVANTAGE. ALSO, ALTHOUGH THE PROCESS IS READILY ACCOMPLISHED AT LARGE MILLS THE PURCHASE OF BOTH THE FEEDER AND NUTRIENT PREMIX IS A FINANCIAL CHALLENGE FOR SMALLER MILLS. THEREFORE, FLOUR FORTIFICATION IS MORE PRACTICAL IN COUNTRIES THAT MILL FLOUR IN LARGE MILLS RATHER THAN SMALL MILLS. IN 2009 THE WORLD HEALTH ORGANIZATION ISSUED A STATEMENT THAT RECOMMENDED LEVELS OF FORTIFYING FLOUR WITH IRON, ZINC, FOLIC ACID, A AND B 12. IF THE POPULATION CONSUMES — EVEN WOMEN OF CHILD BEARING AGE ARE LIKELY TO BENEFIT. BASED ON 2005 DATA, ABOUT 80% OF THE WORLD’S POPULATION CONSUMES MORE THAN 75 GRAMS OF WHEAT FLOUR A DAY. JUST AS A POINT OF REFERENCE IN THE UNITED STATES WE CONSUME 226 GRAMS OF WHEAT FLOUR A DAY, A HUNDRED GRAMS IN NEPAL AND 430 GRAMS IN IRAN. PRESENTLY 58 COUNTRIES HAVE LAWS THAT MANDATE THE USE OF FOLIC ACID OR IRON IN WHEAT FLOUR. 51 COUNTRIES ADD FOLIC ACID TO WHEAT FLOUR. AS JOE POINTED OUT, FLOUR FORTIFICATION IN OTHER COUNTRIES HAS THE SAME IMPACT THERE THAT WE SEE HERE IN THE UNITED STATES. IT IS ALSO COST EFFECTIVE IN OTHER COUNTRIES. IN 1998 CHILE FORTIFIED WHEAT FLOUR AT 228 MICRO GRAMS AND SAW 41% REDUCTION IN NEURAL TUBE DEFECTS. THE RETURN ON THIS INVESTMENT WAS ABOUT 11 TO 1 FOR EACH $1 SPENT ON FORTIFICATION, $11 WAS AVERTED IN DIRECT COSTS. TO REDUCE NEURAL TUBE DEFECTS GLOBALLY, IN 2004 CDC FORMED THE FLOUR FORTIFICATION INITIATIVE KNOWN AS FFI IN COLLABORATION WITH EMERY UNIVERSITY. IT IS A NETWORK OF GOVERNMENTS AND INTERNATIONAL AGENCIES. WHEAT AND FLOUR INDUSTRIES AND CONSUMER AND CIVIC ORGANIZATIONS TO PROMOTE FLOUR FORTIFICATION. NONE OF THE SECTORS CAN ADDRESS FLOUR FORTIFICATION ALONE. KEY PARTNERS INCLUDE GROUPS LIKE CARGILL AND MILLERS ORGANIZATIONS OR FROM THE PUBLIC SECTOR, WHO AND UNICEF. THE IMPACT OF FFI IS SHOWN HERE. SINCE THE FORMATION OF FFI IN 2004, THE PERCENT OF THE WORLD’S WHEAT FLOUR FORTIFIED IN LARGE MILLS INCREASED FROM 18 TO 30%. NEARLY TWO BILLION PEOPLE HAVE POTENTIAL ACCESS TO FLOUR, ALMOST A ONE BILLION PEOPLE HAVE INCREASED WITH THEIR EXPOSURE SINCE 2004. THE NUMBER OF COUNTRIES FORTIFYING FLOUR INCREASED BY 25. BY 2015 THE TARGET DATE OF THE MILLENNIUM DEVELOPMENT GOALSER, OUR GOAL IS 80% OF THE WORLD’S MILL FLOUR WILL BE FORTIFIED. REACHING THE GOAL HINGES ON INDIA AND CHINA FORTIFYING THEIR FLOUR. TOGETHER, THESE COUNTRIES ACCOUNT FOR 35% OF OF THE WORLD’S POPULATION AND PRODUCE 25% OF THE WORLD’S WHEAT. HOWEVER, IT GOES WITHOUT SAYING THAT REGULATION IN PLACE DOES NOT NECESSARILY LEAD TO OR IMPLY COMPLIANCE. THE CHALLENGES REMAIN. A REGULATORY FRAMEWORK IS NEEDED TO LEVEL THE PLAYING FIELD AND ASSURE QUALITY CONTROL. ALTHOUGH COUNTRIES MAY SEE FORTIFICATION AS AN IMPORTANT CONTRIBUTOR TO NATIONAL DEVELOPMENT, INDUSTRY MAY STILL RESIST REGULATION. MANY COUNTRIES CONTAIN BOTH LARGE AND SMALL MILLS WHEREAS FORTIFICATION IS NOT A MAJOR CHALLENGE FOR A LARGE MILL IT IS AN ECONOMIC CHALLENGE FOR SMALLER MILLS. IN MANY PARTS OF THE WORLD FORTIFICATION IS SEEN AS WITH CONCERN BECAUSE IT CHANGES THE FOOD SPLAY. THIS SHOWS THE NEED FOR AN EDUCATION CAMPAIGN. FLOUR FORTIFICATION IN INDIA AND CHINA IS IMPORTANT BECAUSE OF THE SUBSTANTIAL POPULATION SIZE. FINALLY, ALTHOUGH WE CAN ASSUME THE BENEFITS OF FORTIFICATION IN DEVELOPING COUNTRIES WILL BE COMPARABLE TO THOSE IN THE UNITED STATES, SUCH STUDIES HAVE ONLY BEGUN. MY PLEASURE TO INTRODUCE DR. JOHNSTON. >>GOOD MORNING. I’M RICHARD JOHNSTON. I WANT TO FOCUS ON THE CONCERNS INDICATED ON THIS SLIDE THAT HAVE BEEN RAISED ABOUT THE POSSIBLE RISK OF ADDING FOLIC ACID TO THE FOOD SUPPLY AND ENCOURAGING FOLIC ACID SUPPLEMENTS IN YOUNG WOMEN. AND I WILL SUMMARIZE THE EVIDENCE THAT BEARS ON THOSE CONCERNS. IN SETTING THE UPPER LEVEL OF FOLIC ACID INTAKE, THE INSTITUTE OF MEDICINE, IOM, FOUND REASON FOR CONCERN ONLY ON THE ISSUE OF POSSIBLE PROGRESSION OF NERVE DAMAGE IN B-12-DEFICIENT PATIENTS. CASE REPORTS FROM THE 1940s AND ’50s HAD SHOWN THAT FOLIC ACID DOSES OF 5,000 MICROGRAMS OR MORE COULD ELIMINATE ANEMIA WHILE ALLOWING NEUROLOGIC DAMAGE TO PROCEED. THE IOM ADOPTED 5,000 MICRO GRAMS AS THE LOWEST OBSERVED ADVERSE EFFECT LEVEL TO ALLOW THE TOLERABLE UPPER INTAKE LEVEL OF 1,000 MICRO GRAMS PER DAY. IN DATA FROM THE PERIOD 2003 TO 2006 INDICATED THAT 2.7% OF THE U.S. ADULT POPULATION EXCEEDED 1,000 MICRO GRAMS PER DAY INTAKE, BUT ONLY THOSE WHO CONSUMED GREATER THAN 400 MICRO GRAMS PER DAY AS A SUPPLEMENT EXCEEDED THE UPPER LEVEL. THERE IS NO KNOWN EVIDENCE THAT FOLIC ACID AT CURRENT INTAKE LEVELS HAS HARMED INDIVIDUALS WITH B-12 DEFICIENCY OR PERNICIOUS ANEMIA. IN THE ABSENCE OF DIRECT TOXIC EFFECTS OF FOLIC ACID AT ANY DOSE, ANY IDENTIFIES RISKS TO CHILDREN AND DATA AND TURNOVER IN CHILDREN THE IOM ADJUSTED DOWN THE UPPER INTAKE LEVEL FROM 1,000 MICRO GRAMS PER DAY ON THE BASIS OF RELATIVE BODY WEIGHT. THERE IS NO KNOWN EVIDENCE THAT INTAKE ABOVE THE RECOMMENDED LEVELS HAS HARMED CHILDREN. CONSIDERING THE RAPID GROWTH THAT CHARACTERIZES CHILDHOOD IT’S POSSIBLE THAT HIGHER DOSES OF FOLIC ACID ARE ACTUALLY BENEFICIAL. FOLIC ACID IS CONVERTED TO ITS ACTIVE FORM IN TISSUES. EXCESS UNMETABOLIZED FOLIC ACID ENTERS THE CIRCULATION AND IS EXCRETED. IT’S BEEN REPORTED AFTER INTAKE OF AS LITTLE AS 300 MICRO GRAMS IN A BOLUS. ADULT AND NEWBORN AMERICANS HAVE BEEN EXPOSED TO UNMETABOLIZED FOLIC ACID FOR DECADES. NO HARM HAS BEEN IDENTIFIED. CONCERN HAS BEEN RAISED THAT FOLIC ACID INTAKE COULD INTERFERE WITH METHOTREXATE OR FENATOYN THERAPY. ACCORDING TO STANDARDS OF CARE, BOTH AGENT AS ARE USED OVER WIDE DOSE RANGES AND DOSAGE IS TAILORED TO EACH INDIVIDUAL. THERE IS NO KNOWN EVIDENCE THAT FOLIC ACID INTAKE HAS INTERFERED WITH STANDARD ANTI-FOLATE THERAPY. EARLY STUDIES SUGGESTED THAT PERI CONCEPTIONAL VITAMIN USE WAS ASSOCIATED WITH MORE MULTIPLE BIRTHS AND MISCARRIAGES. HOWEVER, THERE IS NO EVIDENCE FROM SUBSTANTIAL SUBSEQUENT RESEARCH TO INDICATE THAT INCREASED FOLIC ACID INTAKE INCREASES MULTIPLE BIRTHS OR MISCARRIAGES. ELEVATED BLOOD HOMOSISTANE, LOW BLOOD FOLATE OR LOW FOLATE INTAKE HAVE BEEN SHOWN WITH INCREASED RATES OF DEMENTIA IN MOST STUDIES, BUT NOT ALL. PATIENTS WITH LOW B-12 LEVELS BUT RELATIVELY HIGH BLOOD FOLATE LEVELS SCORED MORE POORLY ON MEMORY TESTS. IS THIS DUE TO FOLIC ACID INTERFERENCE WITH B-12 METABOLISM IN SOME WAY? NOT NOW UNDERSTOOD. OR IS IT DUE TO PRECLINICAL PERNICIOUS ANEMIA IN SUPPLEMENT TAKERS WHO ABSORBED FOLATE BUT NOT B-12? 97% OF THOSE WITH NORMAL B-12 AND HIGH BLOOD FOLATE HAD EVIDENCE OF INCREASED COGNITION. THERE IS NO EVIDENCE OF HARM AND SOME EVIDENCE OF BENEFIT, BUT THE DATA ARE CONFLICTING AT THIS POINT. FOLATES ARE A POTENT SOURCE OF METHYL GROUPS. COULD HIGHER FOLIC ACID INTAKE INCREASE METHYLATION OF DNA RESIDUES THAT DECREASE TUMORS OR OTHER DISEASES? PREGNANT MICE FED HIGH DOSES INCLUDING FOLIC ACID DELIVERED OFF SPRING WITH HIGH IN THE COAT COLOR CHANGE. HUMANS GIVEN 5,000 TO 10,000 MICRO GRAMS PER DAY OF FOLIC ACID FOR THREE TO 12 MONTHS HAD INCREASED DNA METHYLATION AND COLO RECK CALL ABNORMAL, BUT FOR SIX MONTHS IT DID NOT MODIFY LYMPHOCYTE DNA. THERE IS NO EVIDENCE OF HARM TO DATE, BUT EPI GENETIC METHYLATION IS PLAUSIBLE. FURTHER RESEARCH IS NEEDED. HIGHER FOLATE STATUS HAS BEEN ASSOCIATED WITH RELATIVE PROTECTION AGAINST SEVERAL CANCERS. PERI CONCEPTIONAL FOLIC ACID SUPPLEMENTS AND FORTIFICATION ARE ASSOCIATED WITH REDUCED RISK OF THREE CHILDHOOD CANCERS IN THREE SEPARATE STUDIES. BUT IN MICE BRED TO DEVELOP COLORECTAL ABNORMUS HIGH DOSE FOLIC ACID DECREASED ABNORMUS THE GIVEN BEFORE FORMATION, BUT INCREASED IF GIVEN AFTER IT HAD FORMED. HUMANS WITH A PRIOR ADNORMA GIVEN FOLIC ACID FOR THREE TO FIVE YEARS HAD AN INCREASED RISK OF RECURRENCE OF THREE OR MORE ADNORMAS. THERE IS NO EVIDENCE OF HARM AT INTAKES RECOMMENDED TO PREVENT NEURAL TUBE DEFECTS, BUT THERE IS A THEORETICAL RISK OF CANCER AT HIGH DOSES IN SUPPLEMENT TAKERS. MORE RESEARCH IS NEEDED. IN SUMMARY, THERE ARE NO DATA TO INDICATE THAT FOLIC ACID CAN CAUSE HARM AT LEVELS IN FORTIFIED FOODS OR AT LEVELS RECOMMENDED TO PREVENT NTDs, BUT THE DATA ARE NOT YET CLEAR WITH INTAKE OF HIGH DOSE SUPPLEMENTS, ESPECIALLY WITH REGARD TO CANCER. FOLIC ACID AT RECOMMENDED DOSES PROBABLY PREVENTS THE OCCURRENCE OF CANCER BUT FOLIC ACID AT HIGHER DOSES COULD PROMOTE THE GROWTH OF EXISTING MALIGNANCY. CONTINUED MONITORING AND RESEARCH ARE CLEARLY NEEDED TO AVOID THE POTENTIAL HARM IN ANY FORM, BUT IT SHOULD BE EMPHASIZED PREVENTION OF NEURAL TUBE DEFECTS BY PERI CONCEPTIONAL FOLIC ACID IS PROVEN AND AN ESTIMATED 150,000 NEURAL TUBE DEFECTS PER YEAR COULD BE PREVENTED WORLDWIDE BY ADEQUATE FORTIFICATION OF FOODS WITH FOLIC ACID. DR. LAYTON? >>GOOD MORNING. THANK YOU. I’M JESSICA LAYTON, THE SENIOR ADVISER FOR SCIENCE AT FDA’S NEW OFFICE OF FOODS. MY GOAL TODAY IS TO PROVIDE BASIC INFORMATION ON FOLIC ACID FORTIFICATION AND I’M ALSO GOING TO LAY OUT SOME OF THE NEXT STEPS THAT WOULD NEED TO BE TAKEN IF ADDITIONAL FORTIFICATION IS BEING CONSIDERED. FIRST, I WANT TO GIVE A BRIEF OVERVIEW OF FOLIC ACID FORTIFICATION. MANUFACTURERS CANNOT ARBITRARILY ADD FOLIC ACID TO FOODS WITHOUT HAVING FDA REGULATORY APPROVAL. CURRENTLY, FORTIFICATION IS REGULATED BOTH AS A FOOD STANDARD AND AS A FOOD ADDITIVE. UNDER FDA FOOD STANDARD REGULATIONS, CERTAIN FOODS SUCH AS ENRICHED CEREAL GRAIN PRODUCTS HAVE STANDARDS OF IDENTITY. THESE STANDARDS DEFINE A FOOD PRODUCT, ITS NAME A AND THE INGREDIENTS USED IN THE FOOD AND THEY ALSO MAY INCLUDE SOME CRITERIA FOR HOW THE FOOD IS MANUFACTURED. OTHER FOODS ARE FORTIFIED WITH FOLIC ACID AS FOOD ADDITIVES UNDER THE FOOD ADDITIVES REGULATION. FOOD ADDITIVES ARE SUBSTANCES WHOSE INTENDED USE RESULTS IN THE ADDITIVE BECOMING A COMPONENT OR AFFECTING THE CHARACTERISTIC OF THE FOOD. THE STANDARD OF IDENTITY FOR ENRICHED FLOUR WAS ESTABLISHED IN 1941. ENRICHMENT OF FLOUR IS NOT MANDATORY, BUT IF A PRODUCT CLAIMS TO BE ENRICHED THEN THE FLOUR MUST CONTAIN ALL OF THE INGREDIENTS REQUIRED TO BE CALLED ENRICHED. UNTIL ABOUT TEN YEARS AGO THAT INCLUDED THIAMIN, RIBOFLAVIN, NIACIN AND IRON. IN 1996 THERE WAS A REGULATION WHICH BECAME EFFECTIVE IN 1998, AS YOU HAVE HEARD. AS PART OF THAT REGULATION, FOLIC ACID WAS ADDED AS ONE OF THE MANDATED INGREDIENTS IF A PRODUCT WAS TO BE LABELED AS AN ENRICHED CEREAL GRAIN PRODUCT. THE REGULATION PROVIDED FOR FORTIFICATION AS A FOOD ADDITIVE OF BREAKFAST CEREALS AND DIETARY SUPPLEMENTS. WHAT IF WE WANTED TO FORTIFY OTHER FOODS WITH FOLIC ACID? THERE ARE A NUMBER OF ISSUES THAT MUST BE ADDRESSED WHEN WITH FORTIFICATION FOR CERTAIN NUTRIENTS IS CONSIDERED. IN GENERAL, WE LOOK AT WHETHER THERE IS PUBLIC HEALTH NEED THAT CAN BE ADDRESSED BY THE FORTIFICATION. WE LOOK AT THE SCIENTIFIC ISSUES RELATED TO IMPLEMENTING FORTIFICATION OF THE FOOD SUPPLY. WE LOOK AT WHETHER THERE ARE SAFETY ISSUES THAT CAN RESULT FROM FORTIFICATION. AND WE LOOK AT HOW WE CAN MONITOR THE EFFECTIVENESS AND SAFETY OF THE FORTIFICATION. FIRST AND KEY IS THE PUBLIC HEALTH NEED. SINCE 1996 WHEN REGULATIONS WERE PASSED TO FORTIFY WITH FOLIC ACID WE HAVE SEEN A DECLINE OF SPINA BIFIDA AND ANCEPOPHOLY AS A YOU HAVE SEEN. BUT WHILE THE INCIDENCE HAS DECLINED HISPANIC WOMEN HAVE A 20% HIGHER RISK OF A NEURAL TUBE DEFECT-AFFECTED PREGNANCY. BECAUSE THERE ARE OTHER RISK FACTORS FOR NEURAL TUBE DEFECTS FOLIC ACID FORTIFICATION WILL LIKELY NOT PREVENT ALL OCCURRENCES OF NEURAL TUBE DEFECT. WE DON’T KNOW WHETHER THE CURRENT FORTIFICATION LEVEL HAS PREVENTED ALL OF THE NEURAL TUBE DEFECTS THAT CAN RESULT FROM IMPROVEMENTS IN FOLIC ACID INTAKE. AN IMPORTANT QUESTION IS THEN HOW MUCH FOLIC ACID SHOULD BE ADDED TO REDUCE THE FOLIC ACID-SUSCEPTIBLE NEURAL TUBE DEFECTS. SO THIS SLIDE SUMMARIZES THE DECLINE IN THE PREVALENCE OF WOMEN AGES 15 TO 45 YEARS WITH LOW RED BLOOD CELL FOLATE CONCENTRATION. YOU CAN SEE ON THE LEFT AXIS IS THE LEVEL — PERCENT OF RED BLOOD CELLS BELOW 140 MICRO GRAMS PER MILLILITER — NANOGRAMS PER LITTLE LITER, SORRY. AND THIS IS THE CONCURRENT DECLINE IN SPINA BIFIDA AFTER THE FOLIC ACID FORTIFICATION BEGAN. THAT’S THE DOTTED LINES. INTERESTINGLY, YOU CAN SEE THAT HISPANIC WOMEN AND NONHISPANIC WHITE WOMEN CURRENTLY HAVE A SIMILAR PREVALENCE OF LOW BLOOD FOLATE CONCENTRATION WHILE NONHISPANIC BLACK WOMEN ARE MORE DEFICIENT. HOWEVER, RATES OF SPINA BIFIDA ARE LOWEST IN THE BLACK WOMEN. THE SECOND SET OF ISSUES RELATES TO THE IMPLEMENTATION OF FOLIC ACID FORTIFICATION. FIRST, WHAT ADDITIONAL FOODS COULD BE FORTIFIED? VARIOUS INDUSTRY AND ADVOCACY GROUPS, CDC AND FDA, HAVE BEEN IN DISCUSSIONS ABOUT THE POSSIBILITY OF FORTIFYING CORN MA MASS A FLOUR. IT’S CREATED FROM CORN BOILED IN A LIME SOLUTION AND IT’S DIFFERENT FROM CORNFLOWER WHICH DOESN’T HAVE THE LIME SOLUTION. IT’S FOUND IN MANY FOODS INCLUDING TORTILLAS AND TACO SHELLS, CORN CHIPS, ENCHILADA AND CHALUPA. CURRENTLY IT DOES NOT PERMIT FORTIFICATION OF CORN MASA FLOUR AND A THERE IS NO STANDARD OF IDENTIFY FOR THE FLOUR. ANOTHER QUESTION TO BE ADDRESSED IS HOW MUCH FOLIC ACID SHOULD BE ADDED TO ACHIEVE THE FINAL LEVELS DESIRED IN FLOUR? FIRST WE NEED TO UNDERSTAND HOW MUCH FOLIC ACID EXISTS NATURALLY IN CORN MASA FLOUR. ALSO, THERE IS A CONCERN THAT FOLIC ACID IS NOT STABLE IN PRODUCTS IN AN ENVIRONMENT THAT IS MORE ALKALINE. BECAUSE CORN MASA FLOUR IS MADE BE LINE, THE ISSUE OF STABILITY IS OF SOME CONCERN. ANOTHER CONCERN IS WHETHER THE PRODUCT WILL BE ACCEPTED BY CONSUMERS. ONE MUST CONSIDER ANY RESULTING CHANGES IN FLAVOR, COLOR OR TEXTURE. CULTURAL PREFERENCES MUST BE CONSIDERED SINCE CERTAIN POPULATIONS MAY BE SUSPICIOUS OF FORTIFICATION. EXPERIENCE WITH WHEAT FLOUR CAN BE FOR CORN MASA FLOUR. WE ALSO NEED TO CONSIDER SAFETY. SAFETY IS CRITICAL IN THE ASSESSMENT OF WHETHER AND HOW MUCH TO FORTIFY. FIRST WE WANT TO DO NO HARM. REGULATORY DECISIONS ABOUT WHETHER FOLIC ACID CAN BE ADDED TO FOODS ARE BASED ON THE FOOD ADDITIVE SAFETY STANDARD. THIS STANDARD DOES NOT CONSIDER RISK BENEFIT. IT ONLY CONSIDERS SAFETY ISSUES. THERE NEEDS TO BE EVIDENCE OF A REASONABLE CERTAINTY OF NO HARM. FINALLY, WE MUST CONSIDER HOW WE WILL MONITOR AND ENFORCE. MONITORING EFFECTIVENESS WILL REQUIRE CONTINUED ASSESSMENT OF FOLIC ACID INTAKE FROM ALL SOURCES. BLOOD FOLATE CONCENTRATIONS AND NEURAL TUBE DEFECTS IN SUBPOPULATIONS. MONITORING WILL ALSO REQUIRE ONGOING REVIEW OF ANY ADDITIONAL STUDIES AND/OR REPORTS RELATED TO A POTENTIAL HEALTH CONCERN AND SAFETY. MONITORING ALSO REQUIRES HAVING SCIENTIFICALLY VALIDATED METHODOLOGIES TO ANALYZE CORN MASA FLOURS AND THE PRODUCTS FOR QUALITY CONTROL FOR THE INDUSTRY AND THE FDA IN ITS ENFORCEMENT ROLE. SO WHAT NEEDS TO BE DONE IF WE ARE CONSIDERING FORTIFICATION OF CORN MASA FLOUR? TO ADD FOLIC ACID TO FOODS NOT IN THE CURRENT REGULATIONS WOULD REQUIRE CHANGES TO EXISTING FDA REGULATIONS. THIS REQUIRES SUBSTANTIAL SAFETY AND TECHNOLOGY ASSESSMENTS. THE INFORMATION NEEDED INCLUDES A DMON THAT THE FOLIC ACID ADDITION IS SAFE WITH A REASONABLE CERTAINTY OF NO HARM. CAREFUL ANALYSES OF ALL AVAILABLE DATA TO DEVELOP A BEST POSSIBLE ESTIMATE OF THE POTENTIAL EFFECTS OF PROPOSED FORTIFICATION, THE AMOUNT OF ADDITIVES PROPOSED FOR USE AND THE RATIONALE FOR THE AMOUNT AND A DESCRIPTION OF METHODS TO DETERMINE THE AMOUNT OF FOOD ADDITIVE IN RAW, PROCESSED OR FINISHED FOODS. ADDITIONAL ISSUES THAT MUST BE ADDRESSED TO DETERMINE WHETHER CORN MASA FLOUR SHOULD BE FORD IDENTIFIED CONTINUES DETERMINATION OF OF THE SHELF OF LIFE OF FOLIC ACID ADDED TO THE FLOUR, ASSESSMENT OF WHETHER THERE ARE ACCEPTANCE ISSUES AND DEVELOPMENT OF THE VALIDATED METHODS FOR THE ANALYSIS OF FOLIC ACID AND STANDARDS FOR INDUSTRY TO ENSURE PRODUCTACCURACY. SO IN SUMMARY, I THINK WHAT WE HAVE HEARD TODAY IS THAT FORTIFICATION OF FLOUR WITH FOLIC ACID HAS BEEN A HUGE PUBLIC HEALTH SUCCESS STORY IN IMPROVING BOTH FLOOD FOLATE CONCENTRATIONS AND REDUCING NEURAL TUBE DEFECTS. NEURAL TUBE DEFECTS ARE PROBLEMS PEOPLE LIVE WITH THROUGHOUT THEIR WHOLE LIVES. ADDITIONAL FORTIFICATION OF FOODS WITH FOLIC ACID MAY REDUCE THE DISPARITIES IN THE REMAINDER OF THE EXISTING NEURAL TUBE DEFECTS ARE FOLIC ACID-SUSCEPTIBLE. WHAT ARE THE NEXT STEPS? BECAUSE THE TESTS ARE NOT SIMPLE POST COLLABORATION IS ESSENTIAL. IT NEEDS TO INCLUDE THE FDA, CDC AND OTHERS AND THE RESPECTIVE ROLES OF THE GROUPS MUST BE CLEARLY DEFINED. PUBLIC HEALTH CONSENSUS ON APPROPRIATE SOLUTIONS AND SAFETY ISSUES WILL NEED TO BE IDENTIFIED BY CDC, NIH AND THE SCIENTIFIC COMMUNITY. THIS COULD INVOLVE A CONSENSUS WORKSHOP TO ADDRESS THE PUBLIC HEALTH NEED AND SAFETY ISSUE. FOOD TECHNOLOGY RESEARCH THAT ADDRESSES ACCEPTANCE AND STABILITY OF PRODUCT, AND ANALYSIS ISSUES WILL NEED TO BE CONDUCTED BY THE INDUSTRY WITH FDA AND SCIENTISTS. FDA’S ROLE IN THE REGULATORY PROCESS IS TO EVALUATE INFORMATION TO ENSURE REGULATORY ISSUES ARE ADDRESSED, ALL OF THE INFORMATION REQUIRED FOR THE PREPARATION OF A REGULATION WILL NEED ASSISTANCE FROM ALL PARTNERS. WE REALLY LOOK FORWARD TO WORKING WITH ALL OF OUR PARTNERS IN THE FUTURE TO CONTINUE THE REDUCTION OF NEURAL TUBE DEFECTS. THANK YOU FOR HAVING ME HERE TODAY. [ APPLAUSE ] >>COULD YOU IDENTIFY YOURSELF, TOM SINKS, PLEASE? [ LAUGHTER ] [ INAUDIBLE QUESTION ] >>I HAVE TWO QUESTIONS FOR YOU. ONE IS JESSICA DID A GREAT JOB OF SHOWING SOME REALLY IMPORTANT EVIDENCE FROM HANES ON SERUM LEVELS. I WONDER HOW WE’RE LOOKING AT THAT DATA AND CONSIDERING THE NEED TO CONTINUE FORTIFYING FOR HISPANICS WHEN IT LOOKS LIKE WE HAVE BEEN SUCCESSFUL AT FOLATE SUFFICIENCY FOR THE GROUP? THE SECOND ONE IS WHAT’S OUR CURRENT RECOMMENDATION FOR SUPPLEMENTATION? >>WE HAD A 2010 OBJECTIVE THAT ACTUALLY SET A GOAL OF A CERTAIN LEVEL OF RBC FOLATE FOR 50% OF THE POPULATION. IT TURNED OUT TO BE ABOUT 220 NANOGRAMS PER ML. HISPANICS AND NONHISPANIC WHITES ATTAINED THE GOAL. NONHISPANIC BLACKS DID NOT. WE WERE SURPRISED THAT WE ATTAINED THE GOAL SO QUICKLY. VERY QUICKLY AFTER FORTIFICATION. IT HAD SOME VERY INTERESTING SCIENTIFIC ISSUES WE WANTED TO LOOK AT IN TERMS OF HOW METABOLISM OF FOLIC ACID IN FORTIFIED FOODS MIGHT BE DIFFERENT THAN IN SUPPLEMENTS. NEVERTHELESS, WHEN WE DID THAT, WE SET A CONSERVATIVE STANDARD OF 50%. WHAT WE WOULD LIKE TO HAVE IS FOLATE SUFFICIENCY IN 90% OF THE POPULATION. THAT MEANS WE HAVE TO CONSIDER THE POSSIBILITIES OF OTHER WAYS TO INCREASE FOLATE STATUS IN WOMEN OF REPRODUCTIVE AGE. WE REALLY HAVE SPENT TIME TRYING TO INCREASE CONSUMPTION THROUGH EDUCATING WOMEN OF REPRODUCTIVE AGE ABOUT CONSUMING SUPPLEMENTS BUT WE HAVEN’T DONE AS GOOD A JOB AS WE WANTED TO. SO WE’RE HOPING WE CAN LOOK AT SOME OTHER APPROACHES INCLUDING PERHAPS OTHER KINDS OF FORTIFICATION IN OTHER FOODS OR ACTUALLY THINKING ABOUT WHETHER IT’S SAFE TO INCREASE FORTIFICATION IN EXISTING FORTIFIED PRODUCTS. THOSE ARE SOME POSSIBILITIES. TOM, THE QUESTION WAS RECOMMENDATION FOR SUPPLEMENTS? IT’S UNCHANGED. 1992 AND 1998 AND CURRENTLY THE U.S. PREVENTATIVE SERVICES TASK FORCE IN 2009 RECOMMEND THE USE THAT WOMEN OF CHILDBEARING AGE CONSUME 400 MICRO GRAMS OF FOLIC ACID, AT LEAST, DAILY. DID I ANSWER YOUR QUESTION? >>I’D LIKE TO THANK THE PRESENTERS. A QUESTION FOR EITHER DR. JOHNSTON OR DR. LAYTON. I COME FROM A MEDICAL PRODUCT SAFETY BACKGROUND. SO ONE OF THE PRINCIPLES WE START WITH IS THERE IS NO SUCH THING AS A RISK FREE INTERVENTION. THE FDA REGULATORY FRAMEWORK NOTWITHSTANDING, TWO RELATED QUESTIONS. ONE IS — CAN YOU ALL GIVE US A SENSE OF WHAT THE, IF YOU WILL, POST LICENSURE SURVEILLANCE FRAMEWORK IS LIKE? IS THERE A REPORTING SYSTEM? IS IT RESEARCH STUDIES? WHERE IS THAT FURTHER SAFETY MONITORING GOING TO COME FROM? AND, YOU KNOW, WHAT IS THE ACCEPTABLE LEVEL OF RISK? NOT NECESSARILY QUANTIFIABLE BUT GIVEN THE EXPECTED BENEFITS THAT HAVE BEEN — YOU ALL HAVE VERY WELL DOCUMENTED TODAY. WHAT SORT OF TRADE-OFFS FROM A PUBLIC HEALTH STANDPOINT DO YOU FEEL WOULD BE ACCEPTABLE? >>THANK YOU. THOSE ARE PERTINENT QUESTIONS. I’M NOT AWARE THAT THERE IS ANY SURVEILLANCE SYSTEM. IT’S SURVEYED THROUGH RESEARCH STUDIES IN ONE WAY OR ANOTHER. AND THAT’S EXPENSIVE. ONE OF THE CONCERNS THAT WE HAD INITIALLY — THOSE OF US WHO WORKED ON FORTIFICATION AND PARTICULARLY GODFREY, I THINK, WAS THAT THERE WAS NOT FUNDING SET ASIDE FOR RESEARCH ON POSSIBLE RISK. NOW, IN TERMS OF WHAT IS AN ACCEPTABLE LEVEL, I THINK THE FDA WOULD SAY — AND JESSICA CAN CORRECT ME — THAT IF THERE IS A KNOWN RISK YOU PROBABLY SHOULDN’T DO IT. BUT WHERE YOU WILL NEVER BE ABLE TO PROVE THE NEGATIVE. WE CANNOT PROVE EVER THAT THERE IS NO HARM. AND SO FAR THE DATA HAVE RAISED CONCERNS WITH SOME LIELG PLAUSIBILITY, BUT THERE IS NO REAL DATA YET TO INDICATE HARM. I THINK, HOWEVER, NONE OF US WANTS TO HARM THE OLDER POPULATION WHICH WOULD BE THOSE AT RISK WHILE WE ARE BENEFITTING NEWBORN BABIES. AS MUCH AS WE’D LIKE TO BENEFIT THE BABIES. SO WE HAVE TO TRY TO SET THE BALANCE. I THINK THAT’S THE WAY I PERCEIVE IT AS A PERSON WHO’S OUT OF THE REAL ACTION AT THE CDC AND THE FDA. >>THOSE ARE REALLY GOOD QUESTIONS. WHAT IS THE ACCEPTABLE LEVEL OF RISK? I THINK THAT IS SOMETHING THAT WE GRAPPLE WITH EACH TIME WE HAVE SOMETHING THAT MAY HAVE A POTENTIAL RISK. YOU MAY NEVER HAVE A ZERO LEVEL OF RISK. BUT, YOU KNOW, I THINK THAT’S WHAT I WAS TRYING TO SUGGEST. I THINK IT’S MORE OF SOME WISE PEOPLE COMING TOGETHER AND FIGURERING OUT WHAT THAT ACCEPTABLE LEVEL WOULD BE IN THIS SITUATION. THEORETICALLY, YOU KNOW, WE BASICALLY AT FDA HAVE TO LOOK AT THE NO-RISK SITUATION. BUT RECOGNIZING WHAT YOU SAID, YOU KNOW, I THINK THERE IS SOME MEETING OF THE MINDS THAT NEEDS TO BE DONE TO TRY TO FIGURE THAT OUT IN A BETTER WAY. >>THANK YOU. >>CAN I ADD JUST A QUICK EDITORIAL COMMENT? I THINK IF YOU COME TOGETHER AND YOU DECIDE WHETHER THE EVIDENCE INDICATES RISK, YOU’VE GOT TO DO IT WITH A GROUP OF PEOPLE WHO ARE OPEN-MINDED AND WHO WILL FOCUS AS THE NATIONAL ACADEMY AND INSTITUTE OF MEDICINE DO ROUTINELY IN THEIR STUDIES, ON WHAT DO THE DATA SAY? YOU HAVE TO FOCUS ON WHAT THE DATA SAY. REMOVE YOUR BIAS, REMOVE THEORY, REMOVE BIOLOGIC PLAUSIBILITY OR AT LEAST PUT IT IN ITS PLACE IF YOU’RE GOING TO MAKE THAT KIND OF DECISION. >>JIM BEULLER FROM THE PUBLIC HEALTH SURVEILLANCE OFFICE. TWO QUESTIONS. FIRST ARE THERE TRENDS IN THE USE OF INDUCED ABORTION OR PRENATAL DIAGNOSIS THAT COMPLICATE EFFORTS TO MONITOR TRENDS WHEN LOOKING AT LIVE BORN INFANTS AND SECONDLY IT APPEARS THERE IS A LOT OF ROOM FOR IMPROVEMENT IN INCREASING THE USE OF FOLIC ACID VITAMIN SUPPLEMENTS. WHAT SHOULD BE THE ROLE OF PUBLIC HEALTH IN FOSTERING INCREASED VITAMIN USE GIVEN THE FORTIFICATION SITUATION? >>HEAVY DUTY QUESTIONS HERE. OKAY. THE TRENDS IN PRENATAL DIAGNOSIS? SAY IT AGAIN. >>THE TRENDS IN NTDs YOU SHOWED WERE AMONG LIVE BORN INFANTS, I BELIEVE. BUT THERE ARE SOME WOMEN WHO ON PRENATAL DIAGNOSIS WOULD ELECT AN INDUCED ABORTION. ARE THERE TRENDS IN INDUCED ABORTION THAT COMPLICATE THE ABILITY TO MONITOR NTD TRENDS IN LIVE BORN INFANTS? >>THE TRENDS — THE NATIONAL BIRT DEFECTS PREVENTION NETWORK HAS A GROUP OF STATES — ABOUT TEN STATES THAT ACTUALLY DO THE BEST JOB THEY CAN DO WITH PRENATAL DIAGNOSIS. WHEN YOU SEPARATE THOSE TEN STATES OUT OF THE 25 STATES, THE ACTUAL TREND IS THE SAME IN PRENATAL DIAGNOSIS VERSUS NONPRENATAL DIAGNOSIS SYSTEMS. THE DECREASE IS ABOUT 30 35 TO 40% IN BOTH GROUPS. THE DIFFERENCE IS WITH THE PRENATAL DIAGNOSIS STATES THE PREVALENCE IS HIGHER. SO WE CAN SEE THERE ARE HIGHER PREVALENCES WHEN WE CAN GATHER MORE DATA ON TERMINATIONS AND — I’M BLOCKING. WHAT? WELL, STILLBIRTHS AREN’T THAT BIG, BUT WE CAN SEE THAT AND WE CAN USE THAT AS PERHAPS ONE OF THE QUESTIONS THAT I PROPOSED WAS HOW DO WE KNOW WHEN WE HAVE ELIMINATED ALL FOLIC ACID PREVENTABLE BIRTH DEFECTS? WELL, WE WOULD WANT TO USE THOSE STATES OR SYSTEMS THAT HAVE PRENATAL DIAGNOSIS BECAUSE THEY ARE GIVING US A BETTER IDEA OF INCIDENTS RATHER THAN PREVALENCE AND NOT JUST LIMITED TO LIVE BIRTHS. SO DOES THAT ANSWER THE QUESTION? WHAT WAS THE SECOND ONE? >>THE SECOND QUESTION IS GIVEN THE EFFORT TO FORTIFY FOODS, IS THERE A ROLE FOR INCREASING THE USE OF VITAMIN PILLS? >>I THINK WE PREVENTED THE DATA COMPARING HISPANICS AND NONHISPANIC WHITES IN THE USE OF SUPPLEMENTS. I THINK THERE ARE STILL OPPORTUNITIES IN THOSE KIND OF SUBGROUPS LIKE HISPANICS TO PROMOTE THE USE OF SUPPLEMENTS BECAUSE THEY ARE NOT GETTING THE SAME PROPORTION OF SUPPLEMENTS AS OTHER GROUPS. THERE IS AT LEAST ONE STUDY OUT THERE THAT HAS SUGGESTED THAT WHILE WE MAY HAVE ELIMINATED MOST NEURAL TUBE DEFECTS FROM NONHISPANIC WHITE POPULATIONS, THERE IS STILL A POSSIBILITY THAT THERE IS RISK ASSOCIATED THAT WOULD BE AMELIORATED BY THE USE OF SUPPLEMENTS IN THE POPULATION OF HISPANICS. >>TO ADD TO THAT, I THINK WE NEED TO LOOK AT THE DATA FROM THE TEN STATES AS WELL A LITTLE BIT MORE CLOSELY. THE DISPARITIES ARE NOT QUITE AS OBVIOUS WHEN YOU DO THAT. CORRECT ME. AND IT’S BETWEEN THE DIFFERENT RACIAL ETHNIC GROUPS. THE OTHER THING TO NOTE IS THAT THE HISPANIC WOMEN SEEM TO HAVE A LOWER INTAKE OF OF FOLIC ACID TO BEGIN WITH AND EVEN FORTIFYING CORN MASA FLOUR DOESN’T LOOK LIKE IT WOULD GET THEM UP TO THE LEVEL OF 400 MICROGRAMS PER DAY WHICH SPEAKS TO THE CONTINUED NEED FOR DAILY SUPPLEMENTS AS WELL. >>I’M GODFREY OAKLEY FROM EMERY. I WANT TO CONGRATULATE THE SPEAKERS. WHAT A LOVELY DESCRIPTION OF MANY THINGS YOU TALKED ABOUT. IT’S A WONDERFUL PUBLIC HEALTH SUCCESS. IT SEEMS WE ARE WHERE WE WERE WITH POLIO IN 1988. I REMEMBER SEEING STEVE COUCHY’S SLIDE SHOWING THERE WERE 350,000 CASES OF POLIO AND THAT WAS THE IMPETUS FOR CDC TO PROVIDE LEADERSHIP AND MOVE FORWARD TO ACCELERATE THE PACE OF PREVENTION. I HOPE THIS IS THE BEGINNING OF ACCELERATION AND THE PACE OF PREVENTION BECAUSE CDC HAS THE TALENT AND DRIVE. IT MAY NOT HAVE THE MONEY BIT HAS GOOD THINGS IF YOU ADD THE MONEY TO IT TO REALLY ACCELERATE THE PACE AND KEEP KIDS OUT OF WHEELCHAIRS. IT’S EXCITING TO SEE WHAT’S GOING ON HERE. CONGRATULATIONS. >>ARE THERE QUESTIONS FROM THE ENVISION CROWD? NO QUESTIONS FROM OUTSIDE? OKAY, RJ? >>I JUST WANT TO ASK BILL AND JESSICA WHAT OTHER KINDS OF FOODS COULD BE FORTIFIED. WHAT’S KNOWN ABOUT THAT? >>I’LL REFER THAT A TO JESSICA WHO’S MORE OF A FOODIE THAN I AM. >>I DON’T KNOW. >>I THINK WE REALLY NEED TO LOOK AT THE CONSUMPTION IN THE HISPANIC POPULATION IF THAT’S THE POPULATION WE ARE WORRIED ABOUT. AND THERE ARE PROBABLY OTHER FOODS THAT COULD BE FORTIFIED. I’M NOT SURE THAT THEY WOULD HAVE THE SAME LEVEL OF IMPACT. I THINK CORN MASA WAS A GOOD CHOICE CONSIDERING THE CONSUMPTION, BUT I HAVEN’T LOOKED INTO THAT WELL ENOUGH. I DON’T KNOW IF OTHERS HAVE. >>ANOTHER THOUGHT — MAYBE A RANDOM ONE. I DON’T KNOW WHETHER YOU ALL HAVE LOOKED AT FOODS WITH HIGH LEVELS OF FOLIC ACID. IT MIGHT BE FOODS TO PROMOTE THAT WOULD BYPASS THE EXCESS SUPPLEMENT INTAKE AND PROVIDE A MORE NATURAL WAY OF INCREASING FOLIC ACID INTAKE. YOU KNOW, THAT’S ABOUT THE LIMIT OF MY KNOWLEDGE. I KNOW ORANGE JUICE IS A PRETTY GOOD SOURCE OF FOLIC ACID. HAVE YOU MET THE FOOD SUPPLY IN TERMS OF GOOD SOURCES OF — >>NATURAL FOLATES? >>YEAH. >>I MEAN, THE PROBLEM — I DON’T THINK ANYBODY’S GOING TO EAT 44 TOMATOES A DAY. >>YOU CHOSE THOSE BASED ON GOOD CHOICES, RIGHT? >>EXCEPT FOR THE FRIED LIVER. MAYBE IN FRANCE OR SOME PLACE LIKE THAT. ACTUALLY, ORANGE JUICE IS THE MOST ACCESSIBLE FOR FOLATE. THE OTHER FOODS ARE NOT AS ACCESSIBLE. THERE ARE REALLY NO — YOU CAN’T FOCUS ON ANY ONER PARTICULAR FOOD TO INCREASE FOOD FOLATES. ON AVERAGE IN THE UNITED STATES, I THINK THE AVERAGE INTAKE IS 200 MICROGRAMS PER DAY OF FOLATE. TO INCREASE THAT IS A CHORE. NCI HAS BEEN TRYING TO GET YOU ALL TO EAT FIVE A DAY, NOW 11 A DAY. WHAT THEY HAVE FOUND IS IT’S VERY DIFFICULT, NOT ONLY BECAUSE THE FOODS ARE EXPENSIVE BUT IT’S ALSO BECAUSE PEOPLE JUST AREN’T ORIENTED THAT WAY. IF WE COULD GET SOME OF THOSE — WELL, NATURAL FOLATES INTO FOODS THAT ARE NOW THE MOST POPULAR ONES, I THINK THAT WOULD BE A VERY HELPFUL THING. WE JUST WEREN’T ABLE TO DO THAT. THERE IS A NATURAL FOOD AND A PLANT THAT I KNOW EXISTS CALLED AMARANTH. THIS IS A GRAIN. THAT HAS A VERY HIGH FOLATE CONTENT. IT’S NOT SOMETHING USED WIDELY AROUND THE WORLD BUT SOME PLACES ARE TRYING TO PROMOTE THE USE OF THE GRAIN. BECAUSE IT GROWS READILY AND IT’S HIGHLY NUTRITIOUS AND HAS SOME OF THE HIGHER FOLATE CONTENTS THAT EXIST. SO THAT WOULD BE TRYING TO INTRODUCE THOSE NEW FOODS WOULD BE RELATIVELY DIFFICULT. >>I THINK TO FORTIFY FLOUR ON A GLOBAL BASIS, THAT’S LIKE THE KEY POINT, I THINK THERE. >>THE OTHER PROBLEM WITH FOOD IS THE BIOAVAILABILITY ISSUE. >>IN FORTIFYING THE MAJOR STAPLES TO FORTIFY WOULD BE WHEAT FLOUR, CORNFLOWER AND RICE. COSTA RICA FORTIFIES WHEAT FLOUR, CORN FLOUR, RICE AND MILK. THEY PUT FOLATE IN MILK. WE DID STUDIES YEARS AGO LOOKING AT TRYING TO USE COMBINATIONS OF FOODS AND THE FEDERAL REGISTER THAT DESCRIBES THE REGULATIONS FOR FORTIFICATION, THE MODELING LOOKED AT TRYING TO ADD FOLIC ACID TO THREE FOODS — MILK, ORANGE JUICE AND WHEAT FLOUR. IT WAS FOUND IT WOULD BE COMPLICATED TO DO THAT. SO THEY ENDED UP USING JUST WHEAT FLOUR WHICH IS, FOR US, A MAJOR STAPLE. >>I WANT TO THANK EVERYBODY FOR YOUR ATTENTION AND PARTICIPATION. I ALSO ABSOLUTELY WANT TO SAY IT’S BEEN SUCH A PLEASURE TO WORK WITH THESE OUTSTANDING COLLEAGUES WHO, AS YOU HAVE SEEN, HAVE BEEN SO DISCIPLINED ABOUT THE TIME. WE HAVE ALLOWED THIS TIME — ENOUGH TIME FOR DISCUSSION. SO I WOULD LIKE TO THANK EVERYBODY AND SAY WE HAVE A DATE, SAME TIME, SAME PLACE IN FOUR WEEKS. THANK YOU. [ APPLAUSE ]

2 Replies to “Folic Acid in the Prevention of Birth Defects”

  1. Great work on folic acid.

    Fluoride is another possibility when looking for nutrients that might help prevent NTD's and other birth defects. It is number 5 on a list of 16 (you can search for fluoride prevent birth defects ). Of course, folic acid is number one!

    Ray

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