Setting
Specific Proposed Levels
for bioactive compounds:
Recent experiences in China
Prof. Yang Yuexin
China CDC
Chinese Nutrition society
[email protected]
Key information
•
•
•
•
Developing SPL for phytochemicals
Defining the process of SPL
Key elements & results
Limitations & Challenges
History of RDA in China
1938
1955
1976
6
8
15
1988
20
2000
2013
32
>36
First MNR
as the Minimum Nutrient
Requirement for Chinese
people, including 6 nutrients,
protein, carbohydrate, and
vitamins.
RDA
RDA
the Recommended
Dietary Allowances
DRIs
DRIs
Dietary Reference Intak
• Goals of the DRI Expert Committee
1) Revised and Setting Recommended Intake Values – RNI
and AI
-Both RNI and AI are intended to be used as goals in
planning nutritious diets
2) Facilitating Nutrition Research and Policy – EAR
-EAR values for the scientific basis upon which the RNI
values are set
3) Establishing Safety Guidelines – UL
-Identify potentially hazardous levels of nutrient intake
-Indispensable to consumers who take supplements or
consume foods or beverages to which vitamins or
minerals have been added
4)
4) Preventing Chronic Diseases
The DRI committee takes into account chronic disease
prevention, wherever appropriate
-PI ( preventing intake -NCD)
the committee set lifelong intake goals for Na , K ,VitC
at levels believed in the later years
-- Acceptable macronutrient Distribution Ranges (AMDR)
AMDR for FAT , CHO and Protein
- Specific Proposed Level( SPL) , a diet that provides
adequate Non - Nutrients Substance while reducing the
risk of chronic diseases
The DRI committee has made separate
recommendations for specific sets of people (specific
age ranges).
Expert Review Panels: 87 experts in 7 groups
Introduction
Macronutrient
fat-soluble
vitamins 4
water -soluble
vitamins 10
Trace Elements 10
Definition ,methods, formula, application
• E, CHO , Fat, and fat acids: DHA , EPA , n-3
• Protein
• Vit A , Vit E
• Vit D , Vit K
• VitB1, B2 , B6, B12, Folic acid,
• Vit C, Niacin,Choline ,Biotin, Pantothenic acid
• Zinc , Iron , I , se, cobalt
• Cu, Mn, Mo, Cr , F
Macro-elements 6
• Ca , P, Mg , K , Na,
• chloride
Non-nutrient 21
• Water , Fiber
• 18 Phytochemicals
Components of the Dietary Reference Intakes
DRI component
,
Estimated Average
Requirement (EAR)
Reflects the estimated median requirement and is
particularly appropriate for applications related to
planning and assessing intakes for groups of
people.
Recommended Nutrient
Intake (RNI)
Derived from the EAR and intended to cover the
requirements for 97–98 percent of the population.
Adequate Intake (AI)
Used when an EAR/RNI cannot be developed;
average intake level based on observed or
experimental intakes.
Tolerable Upper Intake
Level (UL)
Tolerable Upper Intake Level (UL) Highest
average intake that is likely to pose no risk.
Estimated Energy
Requirement (EER)
Average dietary energy intake predicted to maintain
energy balance in a healthy adult of defined age,
gender, weight, height and level of physical activity
that is consistent with good health.
Description
New Concepts Developed
Component
Description
Acceptable Macronutrient
Distribution Range (AMDR)
An intake range for an energy source
associated with reduced risk of chronic
disease.
Fat , fat acid , CHO, Ca,
Proposed intake (PI)
Dietary Goal for Preventing
Non-communicable Chronic Disease
Na, K, ，
Specific proposed level (SPL)
Dietary level for Preventing Specific chronic
Disease
SPL predicted to maintain health in a healthy
adult.
---non nutrients components
(phytochemicals)
Tolerable Upper Intake Level
(UL)
Tolerable Upper Intake Level (UL) ,Highest
average intake that is likely to pose no risk.
most from NOAEL or LOAEL , or ADI
What is SPLs ?
SPLs : Specific Proposed
Level (abbreviations SPLs).
• SPL and UL are a
comprehensive set of
phytochemical
values for healthy
populations that can
be used for a guide
for the diet.
Principles : The
SPLs reflect the
current state of
scientific knowledge
with respect to nonnutrient guide and
are published as a
series of reports by
the CNS
WHY Setting SPL and UL for Non –nutrients components ?
Foods consist of thousands of different chemicals
- each has the potential of being beneficial, neutral, or
harmful to the body
-some may be beneficial in some ways and harmful in other
-some chemical may exert different effects on different
people or when taken at differing doses or at different
life stages
When considering concentrated supplements of
phytochemicals
-Be aware that any normally beneficial substance, even
water, can be toxic when taken in too high a dose
-Though most naturally occurring substances are safe for
most healthy people when consumed in foods
--adequate and safe dosages been established by
Why use novel concept SPL ?
Difference with nutrient and non nutrient
• Definition Essential nutrient for body with the lack
of symptoms .
And non-nutrient are not, maybe just
lifespan essential
• Substantial scientific database
science required for DRI value
digestion , absorption , metabolism , interaction…..
• Established process
EAR -----X---- RNI or RDA
Intake ----X---- AI , lack FC database
Age group ---X , limitation for infants \children
\\woman。。。
DRIs working Structure
DRI Scientific
Board Committee
Scientific
Advisory
Committee
Expert Review
&working
Panels
DRIs
2013
The Secretary
Group
from literature
•
•
•
•
•
•
•
Non-nutrient substances
Non-nutrient bioactive substances
非营养素生物活性物质
bioactive substances 生物活性物质
Dietary ingredient 膳食成分
Photochemical 植物化合物
Botanical 植物药， deriving from plants
Botanical ingredient 植物有效成分
Extract 提取物
Screening conditions for Non-nutrients components
•
Research data accumulated the abundant firsthand
materials
• in natural foodstuffs.
• The use of large amounts of food industry
• Others
After setting the definition for non-nutrients
components and SPL
non-nutrients substances list
水
water
番茄红素
Lycopene
原花青素
Proanthocyanidins
大豆异黄酮
Isoflavones
植物固醇
Phytosterol
异硫氰酸盐
Isothiocyanates
大蒜素
Allicin, Gallic,
Quercetin
氨基葡萄糖
Glucosamine
姜黄素
Curcumin
r –氨基丁酸
GABA
绿原酸
Chlorogenic acid
a-硫辛酸
alpha-Lipoic Acid (LA)
叶黄素
Lutin
Zeaxanthin
L-肉碱
L-carnitine
膳食纤维
低聚果糖
花色甙
白藜芦醇
儿茶酚（儿茶素
榭皮素（角黄素）
Dietary fiber
FOS
anthhoyanin
Resveratrol
Catechol
Types of study used as a basis for Specific Proposed Level
Hierarchy of evidence:
Scientific data
 Meta-analyses

(Cochrane Collaboration)
 (Health Assessment)

(Cohort studies)
 (RCT）
Approach of Expert Review Panels
The expert panels are responsible for:
1. reviewing the scientific literature concerning specific food
component under study for each life-stage, especially adult
2. considering the roles of nutrients in decreasing the risk of chronic
diseases and health conditions
3. evaluating possible criteria or indicators of adequacy and providing
a rationale for the choice of each criterion
4. estimating the average requirement(s) for each nutrient reviewed
for each life-stage
5. interpreting the current data on nutrient intakes of population
groups
6. reviewing the food resource for each nutrient or component
UL approaches
•
NOEL(no observed effect level)
•
LOEL(lowest observed effect level)
•
OSL(the observed safe level)
•
HOI(the highest observed intake)
How to document an effect
Phytochimecals : Specific Proposed Level
物质作用的不同阶段
SPL obtained by observation or experiment,
non-nutrient dietary ingredients that have
beneficial effect in the prevention of chronic
diseases for healthy
adults
毒性
治疗
稳态
营养
临界
Based Substantial Evidence
and detary Intakes (if )
Scientific data
 Meta-analyses

(Cochrane Collaboration)
 (Health Assessment)

(Cohort studies)
 (RCT）
Example
summary on Curcumin
Author and
year
Pungcharoenkul
2009
Khajehdehi P
2011
Usharani P
Countr
Subjects
y
K 泰国
healthy
adults
24
N (T/C)
T1: 8
T2:8
C: 8
糖尿病病
伊朗 人
T: 20
C: 20
糖尿病病
印度 人
T: 36
C: 36
2008
Sahebkar A
2013
Hanai H
2006
不同人群
Meta分
析
日本 静 止 期 肠
炎病人
T: 133
C: 90
T: 45
C: 44
RCT -meta analysis
durati
on
Dose &
methods
Biomarker
/Results
T1: 姜 黄 素 500mg/d ，
血清氧自由基清除
T2姜黄素1g/d
能力↑、血清总胆
C: 维生素E200IU/d 固醇↓、甘油三酯↓
、
2 m T: 姜黄素500mg/d 与对照组相比，血
C: 0mg/d
清TGF-β↓、IL-8↓、
尿蛋白排出↓
2 m T: 姜黄素300mg/d
与对照组相比，血
C: 0mg/d
清IL-6、TNF-a等
炎症因子↓
7d
2m T: 姜黄素45mg-6g/d 血 清 总 胆 固 醇 、
C: 阿托伐他汀、维 LDL-C、甘油三酯
生素E或安慰剂
和HDL-C水平改变
无统计学意义
6m T: 姜黄素2g/d
肠炎活动指数、内
C: 0mg/d
镜检查指数改善
表3 叶黄素与乳腺癌发生风险研究
carotenoids and reduce risk of breast cancer
N
Long term
study
Subjects
Sweden /
Postmenopau
prospective
sal women
Cui,2008
UK/prospective
绝经后妇女
Cho,2003
美国/前瞻性
绝经前妇女
Author
Larsson
2010
Terry,2002 加拿大/前瞻性
Horn-
美国/前瞻性
Ross2002
Zhang
1999
美国/前瞻性
绝经前妇女
duratio
n (y)
up/lower intake
(µg/d)
End point
1008
9.4
≥3160 vs <1422
活检确诊
2879
7.6
≥2281 vs <1000
临床确诊
714
8.0
5939 vs 1006
临床确诊
9.5
6838 vs1219
临床确诊
2.0
≥1782 vs <576
临床确诊
1452病例
/5239对照
绝经前和
绝经后妇女
711
绝经后妇女
(RR;95%CI)
2697
14.0
vs1376;绝经后:
0.95
(0.78-1.16)
0.93
(0.80-1.07)
0.96
(0.75-1.22)
1.17
(0.90-1.53)
1.2
（0.90-1.60）
0.79
绝经前:8796
绝经前和
relative risk
临床确诊
8796vs 1376
retrospective or prospective cohort
(0.63-0.99)
0.95
(0.82-1.10.)
白藜芦醇生物学功能证据等级
Evidences evaluation
• Examples : Not approved due to lack of substantiation
Resveratrol
Evidence
grading
SPL , not specific recommended,
Cardiovascular
Anti-
Anti -
protective
inflammatory
Cancer
effects
activity,
M
L
L
diabetes
L
UL: recommended for adults (draft )
Group A：
Not necessary.
Group B：
UL 值的建议
Group C： 5
资料限制,Information
insufficient
Water
Lutein
Allicin
Catchiness
Lycopene 50mg/d
Glucosamine
r-GABA
curcumin 180 mg/d
DF
Anthocyanin
Resveratrol 2.5g/d
Isothiocyanates
Proanthocyanin 800mg
Quercetin
phytosterol
Lipoic acid
60 mg/d
l 2.4g-3.9g
Fruit -oligosaccharide 15/d
Soy lsoflavone 80mg
L- carnitine 2000mg/d
Chlorogenic acid
Specific Proposed Level ( SPL) for adults only
Group A :
AI
draft
Group C :
Information
insufficient
Group B
SPL
Water 1.5-1.7L
Soy lsoflavone
50mg
L-carnitine
Fiber
Lutein
6 mg
Resveratrol
Lycopene
18 mg/d
R -GABA
phytosterol
0.8g/d, 1.3g/d()
curcumin
Glucosamine
1g/d , 1.5g
Allicin
Anthocyanin
50mg/d
Chlorogenic acid
Proanthocyanin
200mg/d
LA
25-30 g
Catechins
Iso thiocyanates
FOS
Quercetin
A model to understand for DRIs
PI --Preventing Lifestyle-related
Diseases ; SPL for phytochemicals
PI
The importance of SPLs and UL of Phytochemicals
Scientific significance
1)First time to evaluate data of phytochemicals
2)Further understanding of the absorption,d metabolism,
function
3)Establish the procedure method, puts forward the
guiding value ; first suggested a new concepts .
Temporary Guidence Levels
Social & practical significance
1)To avoid overeating
2)To prevent lifestyle-related diseases
3)To increase the natural life-span of healthy humans.
Evidence based PL
Limitations and Challenges
1. Limited human data regarding Phyto-chmicals in global .
2. Limited data concerning genetic variations to affect Phytonutrients requirements or ….
such as Soy lsoflavone
3. Limited data on the surrogate biomarker to reflect status of
marginal (sub clinical) “ deficiency” as well as progression
of chronic diseases. And in specific vulnerable population
groups .
4. Limited data on food composition database .
food composition are not sufficiently available for
assessment of some phyto-nutrients intake.
For lifespan
to quantify a healthy diet should be not only including
essential nutrients but also others
Acknowledgements
Prof.Chenyx, prof. Zhaify, prof.Yangxg
SPL expert penal
16 experts
Scientific Committee:
15 experts
All experts in working panel
2010—2013
80 more
•
Thanks for your attention
Primary Uses of DRIs
The four primary uses of the DRIs are:
• To assess the intakes of individuals
• To assess the intakes of population groups
• To plan diets for individuals
• To plan diets for groups
Some of the dietary planning activities that are most
relevant to DRI use include dietary guidance, institutional
food planning, military food and nutrition planning,
planning for food-assistance programs, food labeling,
food fortification, developing new or modified food
products, and food-safety assurance.
Primary Uses of SPL and UL
SPLs put on evaluating scientific evidence for the role
played by …, that could contribute to the prevention of the
major diet-related chronic diseases .
Oo perspective has been accounted for in setting the
recommendation
The primary uses of the SPLs and UL are:
• In the prevention of major diet-related chronic diseases
• To assess the intakes of individuals
• For food-safety assurance, during new or functional food
product development
DRIs
Purpose:
• To maintain and promote health
• To prevent lifestyle-related diseases and
illnesses due to insufficient and excessive
consumption of energy and nutrients
Target population : Healthy individuals and groups
Incl. those who have some mild ailments but do not
need dietary restrictions or prescribed diets.
e.g., hypertension, hyperlipidemia.
& SPL