Setting Specific Proposed Levels for bioactive compounds: Recent experiences in China

Transcription

1 Setting Specific Proposed Levels for bioactive compounds: Recent experiences in China Prof. Yang Yuexin China CDC Chinese Nutrition society

2 Key information Developing SPL for phytochemicals Defining the process of SPL Key elements & results Limitations & Challenges

3 History of RDA in China >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

4 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 4) -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

5 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).

6 Expert Review Panels: 87 experts in 7 groups Introduction Definition,methods, formula, application Macronutrient fat-soluble vitamins 4 water -soluble vitamins 10 Trace Elements 10 Macro-elements 6 Non-nutrient 21 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 Ca, P, Mg, K, Na, chloride Water, Fiber 18 Phytochemicals

7 Components of the Dietary Reference Intakes DRI component, Description Estimated Average Requirement (EAR) Recommended Nutrient Intake (RNI) Adequate Intake (AI) Tolerable Upper Intake Level (UL) Estimated Energy Requirement (EER) Reflects the estimated median requirement and is particularly appropriate for applications related to planning and assessing intakes for groups of people. Derived from the EAR and intended to cover the requirements for percent of the population. Used when an EAR/RNI cannot be developed; average intake level based on observed or experimental intakes. Tolerable Upper Intake Level (UL) Highest average intake that is likely to pose no risk. 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.

8 New Concepts Developed Component Description Acceptable Macronutrient Distribution Range (AMDR) Proposed intake (PI) Specific proposed level (SPL) ---non nutrients components (phytochemicals) Tolerable Upper Intake Level (UL) An intake range for an energy source associated with reduced risk of chronic disease. Fat, fat acid, CHO, Ca, Dietary Goal for Preventing Non-communicable Chronic Disease Na, K,, Dietary level for Preventing Specific chronic Disease SPL predicted to maintain health in a healthy adult. Tolerable Upper Intake Level (UL),Highest average intake that is likely to pose no risk. most from NOAEL or LOAEL, or ADI

9 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

10 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

11 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

12 DRIs working Structure DRI Scientific Board Committee Scientific Advisory Committee Expert Review &working Panels The Secretary Group DRIs 2013

13 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

14 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

15 non-nutrients substances list 水膳食纤维低聚果糖花色甙白藜芦醇儿茶酚 ( 儿茶素 water Dietary fiber FOS anthhoyanin Resveratrol Catechol 番茄红素原花青素大豆异黄酮植物固醇异硫氰酸盐大蒜素 Lycopene Proanthocyanidins Isoflavones Phytosterol Isothiocyanates Allicin, Gallic, 榭皮素 ( 角黄素 ) Quercetin 氨基葡萄糖 Glucosamine 姜黄素 Curcumin r 氨基丁酸 GABA 绿原酸 叶黄素 Chlorogenic acid Lutin Zeaxanthin a- 硫辛酸 alpha-lipoic Acid (LA) L- 肉碱 L-carnitine

16 Types of study used as a basis for Specific Proposed Level

17 Hierarchy of evidence: Scientific data Meta-analyses (Cochrane Collaboration) (Health Assessment) (Cohort studies) (RCT)

18 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

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22 UL approaches NOEL(no observed effect level) LOEL(lowest observed effect level) OSL(the observed safe level) HOI(the highest observed intake)

23 How to document an effect

24 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

25 Based Substantial Evidence and detary Intakes (if ) Scientific data Meta-analyses (Cochrane Collaboration) (Health Assessment) (Cohort studies) (RCT)

26 Author and year Pungcharoenkul 2009 Khajehdehi P 2011 Usharani P 2008 Example summary on Curcumin Countr y K 泰国 伊朗 印度 Subjects healthy adults 24 糖尿病病人 糖尿病病人 N (T/C) T1: 8 T2:8 C: 8 T: 20 C: 20 T: 36 C: 36 durati on RCT -meta analysis Dose & methods Biomarker /Results 7d T1: 姜黄素 500mg/d, 血清氧自由基清除 T2 姜黄素 1g/d C: 维生素 E200IU/d 能力 血清总胆固醇 甘油三酯 2 m T: 姜黄素 500mg/d C: 0mg/d 2 m T: 姜黄素 300mg/d C: 0mg/d 与对照组相比, 血清 TGF-β IL-8 尿蛋白排出 与对照组相比, 血清 IL-6 TNF-a 等炎症因子 Sahebkar A 2013 Hanai H 2006 Meta 分析 日本 不同人群 T: 133 C: 90 静止期肠炎病人 T: 45 C: 44 2m 6m 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 T: 姜黄素 2g/d C: 0mg/d 肠炎活动指数 内镜检查指数改善

27 表 3 叶黄素与乳腺癌发生风险研究 carotenoids and reduce risk of breast cancer Author Long term study Subjects N duratio n (y) up/lower intake (µg/d) End point relative risk (RR;95%CI) Larsson 2010 Sweden / prospective Postmenopau sal women vs <1422 活检确诊 0.95 ( ) Cui,2008 UK/prospective 绝经后妇女 vs <1000 临床确诊 Cho,2003 美国 / 前瞻性绝经前妇女 vs 1006 临床确诊 0.93 ( ) 0.96 ( ) Terry,2002 加拿大 / 前瞻性绝经前妇女 1452 病例 /5239 对照 vs1219 临床确诊 1.17 ( ) Horn- Ross2002 美国 / 前瞻性 绝经前和 绝经后妇女 vs <576 临床确诊 1.2 ( ) Zhang 1999 美国 / 前瞻性 绝经前和 绝经后妇女 绝经前 :8796 vs1376; 绝经后 : 8796vs 1376 临床确诊 0.79 ( ) 0.95 ( ) retrospective or prospective cohort

28 白藜芦醇生物学功能证据等级 Evidences evaluation Examples : Not approved due to lack of substantiation Resveratrol SPL, not specific recommended, Cardiovascular Antiinflammatory Anti - diabetes protective effects activity, Cancer Evidence grading M L L L

29 UL: recommended for adults (draft ) Group A: Not necessary. Water Catchiness r-gaba Anthocyanin Group B: UL 值的建议 Lutein 60 mg/d Lycopene 50mg/d curcumin 180 mg/d Resveratrol 2.5g/d Proanthocyanin 800mg phytosterol l 2.4g-3.9g Fruit -oligosaccharide 15/d Soy lsoflavone 80mg L- carnitine 2000mg/d Group C: 5 资料限制,Information insufficient Allicin Glucosamine DF Isothiocyanates Quercetin Lipoic acid Chlorogenic acid

30 Specific Proposed Level ( SPL) for adults only AI Group A : Water Fiber L g Group B SPL Soy lsoflavone Lutein Lycopene phytosterol Glucosamine Anthocyanin Proanthocyanin 50mg 6 mg 18 mg/d 0.8g/d, 1.3g/d() 1g/d, 1.5g 50mg/d 200mg/d draft Group C : Information insufficient L-carnitine Resveratrol R -GABA curcumin Allicin Chlorogenic acid LA Catechins Iso thiocyanates FOS Quercetin

31 A model to understand for DRIs PI --Preventing Lifestyle-related Diseases ; SPL for phytochemicals PI

32 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

33 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.

34 For lifespan to quantify a healthy diet should be not only including essential nutrients but also others

35 Acknowledgements Prof.Chenyx, prof. Zhaify, prof.yangxg SPL expert penal 16 experts Scientific Committee: 15 experts All experts in working panel 80 more

36 Thanks for your attention

37 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.

38 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

39 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