DIETARY  REFERENCE  INTAKES  IN  THE  UNITED  STATES  Taylor  C.  Wallace,  PhD,  CFS,  FACN  

October  27th,  2014  

Disclosures  

•  Employment  –  George  Mason  University,  Department  of  Food  and  NutriKon  Studies  

–  Dr.  Taylor  Wallace  –  Food  &  NutriKon  Blog  –  NaKonal  Osteoporosis  FoundaKon  –  NaKonal  Bone  Health  Alliance  

 

•  Familiarize  yourself  with  bioacKves.  1  

• Understand  the  DRI  process.  2  

• Discuss  why  DRIs  are  needed  for  bioacKves?  3  

Today’s  Overview    

•  Explore  the  current  DRIs  for  dietary  fiber.  4  

Nutrient  

•  Substance  that  provides  structural  or  funcKonal  components  or  energy  to  the  body.  

•  Examples:  vitamins,  minerals,  protein,  carbs,  fat,  water  and  etc.  

•  EssenKal  nutrients  vs.    non-­‐essenKal  nutrients  

Essen7al  Nutrient  

•  Substances  that  must  be  obtained  from  the  diet  because  the  body  cannot  make  it  in  sufficient  quanKty  to  meet  its  needs.    

•  Absence  results  in  a  deficiency  disease  (e.g.  vitamin  C  and    scurvy).  

Bioac7ves  

•  Compounds  that  are  consKtuents  in  foods  and  dietary  supplements,  other  than  those  needed  to  meet  basic  human  nutriKonal  needs,  which  are  responsible  for  changes  in  health  status.  NIH,  Federal  Resister,  Vol  69,  No.  179:  Sept.  16,  2004,  pp  55821-­‐2.  

•  Examples:  –  Avenanthramides  in  oats  –  Anthocyanins  in  blueberries  –  Lutein  in  spinach  

Bioac7ves  

•  Are  typically  absorbed  from  the  diet.      

•  May  be  considered  part  of  healthy  diet  (e.g.  a  diet  rich  in  colorful  fruits  and  vegetables).      

•  Absence  does  not  result  in  a    deficiency  disease.    

Bioac7ves  

•  Widely  distributed  in  nature  and  the  diet.  

•  Generally  thought  to  be  safe  at  normal  nutriKonal  consumpKon  levels.  

•  Content  in  food  is  extremely  variable  based  on  environmental  condiKons  (e.g.  temperature,  alKtude,  soil  acidity  and  etc.).  

•  Some  more  well  characterized  than  others…  

Drugs  ≠  Nutrients  ≠  Bioac7ves  

Parameter   Drugs   Nutrients   Bioac7ves  

Chemically  defined  and  well  characterized  

Yes,  single  enKKes  

Yes,  single  enKKes    

No,  complex  mixtures  

EssenKality   None   EssenKal   Unclear  

Inadequacy  results  in  disease  

No   Yes   No  

True  placebo  group   Yes   No   No  

Targets   Single  organ  or  Kssue  

All  cells  and  Kssues  

MulKple  cells  and  Kssues  

SystemaKc  FuncKon   Isolated   Complex  networks  

Complex  networks  

Adapted  from:  Heber  D  and  Shao  A  (2011)  

Drugs  ≠  Nutrients  ≠  Bioac7ves  

Parameter   Drugs   Nutrients   Bioac7ves  

Baseline  status  affects  response  to  intervenKon  

No   Yes    

Unclear  

Effect  size   Large   Small   Small  to  moderate  

Side  effects   Large   Small   Small  

Nature  of  effect   TherapeuKc     PrevenKve   PrevenKve  and  therapeuKc  

Adapted  from:  Heber  D  and  Shao  A  (2011)  

Bioac7ves  =  Unique  Characteris7cs  

•  Their  structure,  funcKon(s),  biological  acKvity  may  be  defined  as  a  class  of  compounds    (e.g.  avenanthramides  in  oats).  

•  Classes  are  typically  found  in  similar  types  of  foods  (e.g.  anthocyanins  in  raspberries  and  blackberries)  

•  OpKmal  effects  may  be  achieved  through  consumpKon  of  mixtures  where  the  exact  idenKty  and  composiKon  is  oeen  unknown.  

Dietary  Reference  Intakes  

•  Reference  values  that  are  quanKtaKve  esKmates  of  nutrient  intakes  to  be  used  for  planning  and  assessing  diets  for  healthy  people.  They  include  both  recommended  intakes  and  upper  limits  as  reference  values.    

•  DRI  values:  –  EsKmated  Average  Requirement  (EAR)  –  Recommended  Dietary  Allowance  (RDA)  –  Adequate  Intake  (AI)  –  Tolerable  Upper  Intake  Level  (UL)    

Why  DRIs  are  Important!  

Standards   Science  Review   Programs  Policy  

Es7mated  Average  Requirement    (EAR)  

•  The  average  daily  nutrient  intake  level  that  is  esKmated  to  meet  the  requirements  of  half  of  the  healthy  individuals  in  a  parKcular  life  stage  and  gender  group.  

Recommended  Dietary  Allowance  (RDA)  

•  The  average  daily  dietary  nutrient  intake  level  that  is  sufficient  to  meet  the  nutrient  requirements  of  nearly  all  (97.5%)  healthy    individuals  in  a  parKcular    life  stage  and  gender  group.  

Adequate  Intake  (AI)  

•  The  recommended  average  daily  intake  level  based  on  observed  or  experimentally  determined  approximaKons  or  esKmates  of  nutrient  intake  by  a  group  (or  groups)  of  apparently  healthy  people  that  are  assumed  to  be  adequate.    

•  Used  when  an  RDA  cannot  be  determined.  

Tolerable  Upper  Intake  Level  (UL)  

•  The  highest  average  daily  nutrient  intake  level  that  is  likely  to  pose  no  risk  of  adverse  health  effects  to  almost  all  individuals  in  the  general  populaKon.  As  intake  increases  above  the  UL,  the  potenKal  risk  of  adverse  effects  may  increase.    

•  An  “uncertainty  factor”  can  be  applied  (e.g.  vitamin  D  UL  is  4,000  IU  and  NOAEL  is  10,000  IU).  

Dietary  Reference  Intakes  

DRIs  –  Life  Stage  and  Gender  Groups  

•  Values  are  typically  extrapolated  for  many  age  and  gender  groups  (e.g.  children).  

Prevalence  of  Exceeding  UL  at  4-­‐8  y.  

0

10

20

30

40

Calcium Copper Iron Selenium Zinc

% >

UL

Food Only

Food + MVMM

Wallace  TC,  et  al.  (2012)  

Framework  for  Developing  DRIs  •  Availability  of  data  and  current  research  to  inform  the  commilee  deliberaKons.  –  Data  is  oeen  limited  (e.g.  vitamin  E).  –  Dose  response  data  are  key.  

•  IOM  does  not  typically  generate  basic  data.  

•  Framework  is  recognized  as  akin  to  a  risk  analysis,  which  analyzes  and  controls  the  “risks”  that  may  be  experienced  by  a  populaKon  of  interest.    In  DRI  development  the  risk  is  that  nutrient  intakes  are  too  low  or  high.  

Framework  for  Developing  DRIs  

•  Although  the  reference  values  are  based  on  data,  the  data  are  oeen  scanty  or  drawn  from  studies  that  had  limitaKons  in  addressing  the  quesKon.  

•  Ethical  consideraKons…  

Framework  for  Developing  DRIs  

•  Funding  and  staff  resources.  –  Approximately  $250K  to  review  a  single  nutrient.  –  IOM  can  only  take  <50%  industry  funds  for  a  parKcular  project.  

•  DRIs  as  loose-­‐leaf  notebooks.  

Dietary  Reference  Intakes  (DRIs)  

•  Tables  of  current  DRIs  can  be  found  at:  hlp://www.iom.edu/AcKviKes/NutriKon/SummaryDRIs/DRI-­‐Tables.aspx.    

•  “Framework  for  DRI  Development”  (backgrounder  paper)  can  be  found  at:  hlp://www.iom.edu/AcKviKes/NutriKon/SummaryDRIs/~/media/Files/AcKvity%20Files/NutriKon/DRIs/New%20Material/11Bckgrd%20PaperFramework%20for%20DRI%20Devel.pdf      

“Historically,  the  substances  for  which  nutrient  reference  values  have  been  developed  were  the  essenKal  or  so-­‐called  classical  nutrients,  specifically  vitamins,  minerals,  protein  and  energy  (calories).  As  Kme  has  passed,  substances  found  naturally  in  foods,  ranging  from  fiber  to  carotenoids,  have  been  incorporated  into  the  DRI  process.”  -­‐-­‐  IOM,  2008    

DRIs  for  Bioac7ves  

•  In  1998,  phenols,  polyphenols,  and  flavonoids  were  excluded  from  the  DRI  panel’s  consideraKon  due  to  lack  of  food  composiKon  data  and  knowledge  of  actual  intake  amounts  and  limited  informaKon  on  their  absorpKon  and  metabolism.  –  IOM  Food  and  NutriPon  Board  (1998)  

•  Carotenoids  were  also  reviewed  in  2000  but  were  not  assigned  DRIs.  –  IOM  Food  and  NutriPon  Board  (2000)  

Why  are  DRIs  Important  for  Bioac7ves?    •  BioacKves  would  be  recognized  as  important  for  human  health  and  evaluated  accordingly.    InvesKgators,  regulatory  agencies  and  consumers  would  all  know  how  strong  the  science  was  behind  messaging.      

•  Consumers  and  their  HPCs  would  have  a  target  to  aim  for  in  terms  of  intake.    

•  IncenKve  for  research  to  close  criKcal  gaps.  

Why  are  DRIs  Important  for  Bioac7ves?    

•  Having  a  DRI  value  increases  the  status  of  a  bioacKve  and  makes  it  part  of  nutriKon  public  policy.    

DRIs  Provide  Guidance  for  Claims  

DRIs  Provide  Guidance  for  Claims  

•  2010  Warning  Leler  to  Unilever    –  Lipton  Green  Tea  100%  Natural  Naturally  De-­‐caffeinated  

•  The  claim  “packed  with  flavonoid  anKoxidants”  does  not  comply  with  21  CFR  101.54(g)1)  because  no  RDI  has  been  established  for  flavonoids.  

•  Unauthorized  nutrient  content  claim  caused  the  product  to  be  misbranded  under  secKon  403(r)(2)(A)(i)  of  the  Act.  

Establishing  a  Framework  for  Bioac7ves  •  ScienKfic  frameworks  on  which  to  base  intake  recommendaKons  for  essenKal  nutrients  have  been  established.  –  Dietary  Reference  Intakes  (DRIs)  in  US  and  Canada  –  Dietary  Reference  Values  (DRVs)  in  Europe  –  Nutrient  Reference  Values  (NRVs)  published  by  CODEX  Alimentarius  

•  No  real  solidified  framework  exists  for  bioacKves.    So  where  do  we  start???  

Dietary  Fiber:  A  Case  Study  

•  Non-­‐essenKal      

•  Established  an  AI,  but  not  EAR      

•  Based  on  intake  levels  observed  to  prevent  CHD.    Data  included  observaKonal,  clinical,  and  mechanisKc.      

•  ReducKon  of  risk  for  diabetes  used  as  secondary  endpoint  to  support  recommended  intake  levels  .  

Dietary  Fiber:  A  Case  Study  

•  Number  of  epidemiological  studies  showed  individuals  that  consumed  high  amounts  of  dietary  fiber  and  fiber-­‐rich  foods  had  reduced  CHD  risk.    

•  Large  prospecKve  cohort  studies  showed  significant  inverse  relaKonship  between  total  fiber  intake  and  risk  of  CHD,  together  with  evidence  from  clinical  and  mechanis7c  data;  an  AI  for  total  fiber  was  set.    

Role  of  β-­‐glucans  

•  Were  shown  to  help  normalize  blood  lipid  levels  and  specifically  decrease  LDL-­‐cholesterol  (a  validated  biomarker  of  CHD)  in  hypercholesterolemic  individuals.  

•  Dose  response  was  shown  among  individuals  with  mulKple  risk  factors  of  CHD  when  oatmeal  or  oat  bran  (primary  endpoint).  

•  Glucose  responses  were  also  reduced  with  β-­‐glucan  supplementaKon  (secondary  endpoint).  

Lessons  Learned  from  Fiber  

•  Reported  benefits  may  be  due  to  fiber  source,  not  necessarily  fiber  per  se  (e.g.  is  it  the  fiber  or  the  oats?).      

•  Overall  dietary  palern  may  be  responsible  for  CHD  effect.    

•  At  lease  some  of  the  benefits  associated  with  fiber  may  be  due  to  other  food  components  of  fruits,  vegetables,  and  cereal  products  (e.g.  avenanthramides).    

Concluding  Thoughts  

•  Is  a  shie  in  focus  from  disease  risk  reducKon  to  markers  of  health  and  wellness  feasible?    

•  Should  focus  be  on  maintaining  normal  physiological  func7on  throughout  adulthood,  which  then  leads  to  health  promo7on?      

•  MulKple  risk  biomarkers  may  potenKally  be  helpful  if  all  are  showing  the  same  beneficial  effect  on  a  parKcular  health  outcome  (e.g.,  c-­‐reacKve  protein,  various  interleukins,  etc.)    

Concluding  Thoughts  

•  DemonstraKng  reduced  risk  of  disease  with  a  bioacKve  is  more  difficult  than  it  is  to  show  prevenKon  of  a  deficiency  outcome  with  an  essenKal  nutrient.  –  Lupton  JR  et  al.  (2014)  

•  ScienKfic  data  needs  to  demonstrate  consistent  results.  –  needs  to  be  valid,  reliable  &  reproducible.    

•  We  cannot  solely  depend  on  large  RCTs  to  give  us  the  answer.  

THANK  YOU!  Taylor  C.  Wallace,  PhD,  CFS,  FACN  

www.drtaylorwallace.com