Folate and For+fica+on: Understanding the Basics Presented by Lieven Bauwens Secretary General IF Member of Food For+fica+on Ini+a+ve EMT 25th Annual Interna+onal Conference on Spina Bifida and Hydrocephalus Argen+na, 6 June 2014
The Plan… • … folate Importance for health
Sources of Folate
Measuring Intake
Supplement Use
• … flour for,fica,on What is it?
Why is it important?
Global Support & Impact
Best Prac+ces
S-‐Adenosyl-‐ Homocysteine Homocysteine
Food 5-‐methyl
Tetrahydro-‐ folate
5-‐methyl
Tetrahydro-‐ folate
5-‐methyl
Tetrahydro-‐ folate
(Proteins, DNA Lipids, Myelin) Methyl Translerases
5-‐methyl
Tetrahydro-‐ folate
Tetrahydro -‐folate
Uracil For+fied Food or Supplements
Intes+ne
Methionine
Methionine Synthase (B12)
Methylene Tetrahydro -‐folate
Folic Acid
S-‐Adenosyl-‐ Methionine
Dihydro -‐folate Thymidylate synthase
Dihydro -‐folate reductase
Thymine Dihydro -‐folate reductase
DNA Cell Division Folic Acid Gut Wall
Folic Acid Circula+on
Folic Acid Dividing Cells
Folic Acid
Folate is Important for Everyone’s Health • Needed for DNA, RNA and amino acid synthesis required for cell division • Prevents certain types of anemia • Important for maintaining cardiovascular health • Reduces the risk for neural tube defects • May reduce the risk for other congenital defects, au,sm, and others
Rela+onship of Early Pregnancy Maternal RCF to Risk of NTD. NTD Risk per 1000 Births
12! 10!
8! 6! 4! 2! 0! 453! 906! 1360! 1813! (200)! (400)! (600)! (800)!
• Nested case-‐control study with 84 NTD affected pregnancies and 266 controls • Risk was graded throughout the en,re normal RCF range • Increasing the RCF to above 400 µg/L would be highly protec,ve. • Risk is never 0
Red Cell Folate, nmol/L (µg/L)!
Daly et al JAMA 1995
Folate FOOD FOLATE
FOLIC ACID
• Found in liver, dark green • Found in for,fied foods and vegetables, len,ls, beans, oranges, supplements • Water-‐soluble
• Stable
• Bioavailability ~50% in comparison • Bioavailability to folic acid supplement taken on 1. Supplements taken on empty empty stomach stomach~100% 2. Folic acid taken with food ~85%
Folate Intake Europe Average Folate Intake* 450 400
Intake (µg/day)
350 300 250 200 150 100 50 0
*without supplements or for,fied foods
Recommenda+on for Women of childbearing Age
“ It is recommended that women capable of becoming pregnant consume 400 μg* of folate daily from supplements, for=fied foods, or both in addi;on to consuming food folate from a varied diet.” -‐Ins=tute of Medicine * As dietary folate equivalents (DFE)
Preconcep+onal Folic Acid Use 100 90
% Study Participants
80 70 60 50 40
31.5
30
27.6 18.6
20
19.2 12.2
12
Turkey
UK
10 0 Hungary
Norway
Portugal
Spain
1. Paulik E et al. Eur J Obstet Gynecol Reprod Biol. 2009 Jul; 145(1) 49-52. 4. Navarrete-Muñoz EM. Med Clin (Barc). 2010 Nov 13;135(14):637-43. 5. Baykan Z et al. Arch Gynecol Obstet (2011) 283:1249-1253. 2. Nilson R et al. Am J Clin Nutr 2006; 84 : 1134-1141. 6. Brough L. J Hum Nutr Diet. 2009 Apr; 22(2): 100-107. 3. Pinto, E et al. Public Health Nutr. 2009 Jul; 12(7):922-931.
BUT:
Daily Intake of Folic Acid
N= 100
450 400
micro grams
350 300 250 200 150 100 50 0 1
6
11
16 21 26
31 36 41 46 51 56 61 66
71 76 81 86 91 96
Termina+on is not preven+on
Ignoring NTDs is not preven+on NTDs
Other health outcomes: FA deficiency Stroke Heart disease Low birth weight Pre-‐term birth Other birth defects … Au,sm? Cancer occurrence? Cogni,ve decline / Alzheimer?
Preven+on of NTDs Different strategies • Supplementa,on • For,fica,on • Diet • Oral contracep,ve + Folic Acid • Other
Poten+al Solu+on 1: Supplements • Limita,ons: – Cost and inconsistent use – Minority of women use folic acid supplements at the correct ,me for preven,ng NTDs (even when the pregnancy is a planned one) – important rela,on with socio-‐economic background – Prior to concep,on and during the first 12 weeks of pregnancy, women need 400 microgram folate or folic acid per day.
Poten+al Solu+on 2: For+fied flour • Pro
– Effec,ve – Simple and inexpensive – Requires no change in dietary paierns or individual decision – Non-‐discrimina,ng
• Contra – Controversial (myths) – Reach – Challenge of monitoring and enforcing of legisla,on
What is Flour For+fica+on? • For,fica,on adds vitamins and minerals to flour during the milling process so that the foods made with wheat flour are more nutri,ous. • Flour = wheat and maize flour (rice is very different)
Essen+al Nutrients are Lost During the Wheat Milling Process
Adapted from “Wheat in Human Nutri,on” by W.R. Aykroyd and Joyce Doughty Food and Agriculture Organiza,on of the United Na,ons, Rome, 1970.
Why For+fica+on of Cereal Grains? • It is a public health interven,on • It helps address micronutrient malnutri,on by providing nutrients to deficient popula,ons and preven,ng new cases of deficiency • Bread is widely consumed by individuals from all economic backgrounds • It improves diet quality without requiring behavior change • It is inexpensive per person per year
IF Supports For+fica+on
Consensus for For+fica+on
Resolu+on on Birth Defects WHO WHA 63.17 To support Member States in developing na=onal plans for implementa=on of effec=ve interven=ons to prevent and manage birth defects within their na,onal maternal, newborn and child health plan, strengthening health systems and primary care, including improved coverage of vaccina,on against diseases such as measles and rubella, of addressing tobacco and alcohol use among pregnant women and women trying to conceive, and food for=fica=on strategies, for the preven=on of birth defects, and promo,ng equitable access to such services
Success of for+fying flour with folic acid • Eight regional studies from Argen,na, Canada, Chile, South Africa, and the United States report: – 31% to 78% reduced risk of neural tube defects aoer for,fying wheat flour with folic acid – Overall 46% reduc,on in neural tube defects aoer for,fying flour with folic acid Blencowe, H: Folic acid to reduce neonatal mortality form neural tube disorders International Journal of Epidemiology. April 2010 (suppl_1):i110-i121 . Istockphoto
Success of for+fying flour with folic acid Globally, an es,mated 22,000 birth defects were prevented in 2008 -‐ an average of 60 a day -‐ because wheat flour is for,fied with folic acid. However this amounted to just 9% of FA-‐ preventable NTDs.
Bell, Karen N., Oakley, Godfrey P. Update on Prevention of Folic Acid-Preventable Spina Bifida and Anencephaly. Birth Defects Research (Part A): Clinical and Moleculra Teratology. 85 2009:102-107
Global Best Prac+ces To plan a grain for,fica,on program, consider: • Local culture and cereal consump,on • Nutri,onal needs • Industry analysis • Crea,on of a mul,-‐sector na,onal for,fica,on alliance • Legisla,on for mandatory for,fica,on • Monitoring the process and surveillance for birth defects
Role of SB associa+ons • Understanding the issue – NTD registra,on – Food and nutri,on intake
• Understanding the local situa,on • Build and be part of a Na,onal For,fica,on Alliance • Advocacy • Monitoring of the ac,ons undertaken by government
Conclusions • Folate is one of essen,al micronutrients, intake ooen problema,c in women of childbearing age • Rela,onship FA and NTDs is clearly established • There is a rela,onship with FA and other health issues • For,fica,on is a proven strategy to improve FA status in the whole popula,on • AND/AND, not OR/OR • We have already achieved a lot, but s,ll a lot of work needs to be done • Spina Bifida associa,ons are crucial partners in the FA debate
Thank you!