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  

•  …  flour  for,fica,on    

Importance  for  health  

Sources  of  Folate  

Measuring  Intake  

Supplement  Use  

What  is  it?   Why  is  it  important?  

Global  Support  &  Impact  

Best  Prac+ces  

Methionine  Synthase  (B12)  

Food  

5-­‐methyl  Tetrahydro-­‐

folate  

5-­‐methyl  Tetrahydro-­‐

folate  

5-­‐methyl  Tetrahydro-­‐

folate  

5-­‐methyl  Tetrahydro-­‐

folate  

Homocysteine   Methionine  

Dihydro      -­‐folate  

Uracil   Thymine  

DNA  

Cell  Division  

Methylene  Tetrahydro            -­‐folate  

     Tetrahydro            -­‐folate    

Intes+ne   Gut  Wall   Circula+on   Dividing  Cells  

For+fied  Food                        or  Supplements    

Folic  Acid   Folic  Acid   Folic  Acid   Folic  Acid   Folic  Acid  

Dihydro  -­‐folate  reductase  

Dihydro  -­‐folate  reductase  

Thymidylate      synthase  

(Proteins,  DNA  Lipids,  Myelin)  S-­‐Adenosyl-­‐  

Homocysteine  S-­‐Adenosyl-­‐  Methionine          Methyl  

Translerases  

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.    

•  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  

12!

10!

8!

6!

4!

2!

0!453!(200)!

906!(400)!

1360!(600)!

1813!(800)!

Red Cell Folate, nmol/L (µg/L)!

NTD

Risk

per

100

0 Bi

rths

Daly et al JAMA 1995

Folate  

FOOD  FOLATE   FOLIC  ACID  •  Found  in  liver,  dark  green  

vegetables,  len,ls,  beans,  oranges,    •  Found  in  for,fied  foods  and  

supplements  •  Water-­‐soluble   •  Stable  •  Bioavailability  ~50%  in  comparison  

to  folic  acid  supplement  taken  on  empty  stomach  

•  Bioavailability    1.  Supplements  taken  on  empty  stomach~100%  2.  Folic  acid  taken  with  food  ~85%  

Folate  Intake  Europe  

0  

50  

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Intake  (µ

g/da

y)  

Average  Folate  Intake*  

*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    

31.5 27.6

18.6 19.2 12.2 12

0

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20

30

40

50

60

70

80

90

100

Hungary Norway Portugal Spain Turkey UK

% S

tudy

Par

ticip

ants

1. Paulik E et al. Eur J Obstet Gynecol Reprod Biol. 2009 Jul; 145(1) 49-52. 2. Nilson R et al. Am J Clin Nutr 2006; 84 : 1134-1141. 3. Pinto, E et al. Public Health Nutr. 2009 Jul; 12(7):922-931.

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. 6. Brough L. J Hum Nutr Diet. 2009 Apr; 22(2): 100-107.

Daily Intake of Folic Acid

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1 6 11 16 21 26 31 36 41 46 51 56 61 66 71 76 81 86 91 96

mic

ro g

ram

sN=  100  BUT:  

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!