Setting NRVs for Bioactive Compounds
in South Korea:
Current Situation and Future Challenges
Schlosshotel
Kornberg am Taunus
Germany
November 1, 2013
Bioactives: Qualitative NRVs for Lifestage Groups?
CRN-International 4th Scientific Symposium
Namsoo Chang Dept. of Nutritional Science & Food Management
Ewha Womans University
Seoul, Korea
Health benefits of bioactive
compounds
• Stems from knowledge and experience that
humans have accumulated over time in many
culture
• Korean people have been utilizing over ~0000
vegetables, fruits, nuts, legumes, mushrooms,
grains, and foods of marine sources such as fish
and seaweeds
Characteristics of the Korean Diet
• Philosophy: Food = Medicine
• Plenty of vegetables: Variety, amount
• Foods of marine sources: fish & shellfish,
seaweeds
• Fermented food
• Colorful: 5 different color (red, yellow, blue,
white, black)
Adapted from Trujillo, JADA 2006
Health Benefits of Bioactive Food Components
Cell Oxidation
Hemostasis/thrombosis
Epigenetics
Growing consensus in the scientific
community on setting NRVs for
bioactive compounds
• Heber D & Shao A. Bioactive food components: Changing the
scientific basis for intake recommendations. IADSA, 2011
• Bieselski, et al., Nutrient reference values for bioactives: new
approaches needed? A conference report. Eur J Nutr, 2013 (2012
CRN-I conference on NRV, Kronberg im Taunus, Germany)
• Gaine PC, et al. Are dietary bioactives ready for recommended
intakes? Adv Nutr 4:539-41, 2013 (ASN meeting symposium
summary, May, 2013, Boston, USA)
• 11th china Nutrition Science Conference & 2013 China & Korea
Joint International Phytonutrient Symposium on the essential and
non-essential nutrients present and future. (May 2013, Hangzhou,
China)
• CRN-I scientific symposium on Bioactive: qualitative NRVs for life-
stage groups (Nov., 2013, Kronberg im Taunus, Germany)
To set NRVs for nutrients, we need
to have or decide the following:
• DRIs (EAR, RDA, AI, UL)
• What DRI values to use – RDA
– EAR
• Data needed – Intake assessment
– Health benefits
– Risk assessment
• One value for all general population or multiple values to accommodate specific age or physiological stage groups
Procedures for setting NRVs for
nutrients in South Korea (2011)
• Based on RDA
• Nutrients – protein, total fat, saturated fatty acids, carbohydrates,
dietary fiber, cholesterol, sodium
– vitamins & minerals
• Determination of population adjust means (PAMs) – Population groups by age and gender (Using the
population statistical data from the National Statistics Office)
– ∑ (number of population by age & gender x RDA by age & gender)/total number of population
• Comparison of population adjust means and RDAs
• Compared NRVs with ULs
Current (2013) NRVs for nutrients in
South Korea
Nutrients Amount Nutrients Amount Nutrients Amount
Carbohydrates (g) 330 Iron (㎎) 12 Pantothenic acid (㎎) 5
Dietary fiber (g) 25 Vitamin D (㎍) 5 Phosphorus (㎎) 700
Proteins (g) 55 Vitamin E (㎎α-TE) 11 Iodine (㎍) 150
Fats (g) 51 Vitamin K (㎍) 70 Magnesium (㎎) 315
Saturated fats (g) 15 Vitamin B1 (㎎) 1.2 Zinc (㎎) 8.5
Cholesterol (㎎) 300 Vitamin B2 (㎎) 1.4 Selenium (㎍) 55
Sodium (㎎) 2,000 Niacin (㎎ NE) 15 Copper (㎎) 0.8
Potassium (㎎) 3,500 Vitamin B6(㎎) 1.5 Manganese (㎎) 3.0
Vitamin A (㎍ RE) 700 Folate (㎍) 400 Chromium (㎍) 50
Vitamin C (㎎) 100 Vitamin B12(㎍) 2.4 Molybdenum (㎍) 25
Calcium (㎎) 700 Biotin (㎍) 30
Revised, June 5, 2013
NRVs for bioactive
substances
• Lack of a scientific framework on which to
base recommendations
– Not chemically well-defined except a very few,
often mixtures
– Not essential, but provide health benefits
– No/unclear deficiency symptoms
Bioactive food components
• Are frequently used in the health/functional
foods (HFF) or as ingredients for HFF in
South Korea
The Health Functional Food (HFF) Act
• Enacted in 2004 to ensure the safety of health functional foods with certain
health claims for consumer information.
• Definition: A product (form: tablets, capsules, powders, granules, pastes,
gels, jellies, bars) intended for use to enhance and preserve the human
health with one or more functional ingredients or constituents
• In 2008 the scope was extended to include conventional foods and other
diet supplements
Functional ingredients listed in the
Health/Functional Food Code (Generic type)
Nutrients Non-nutrients
Vitamin A
Vitamin D
Vitamin E
Vitamin K
Beta-carotene
Vitamin B1
Vitamin B2
Vitamin B6
Vitamin B12
Niacin
Vitamin C
Pantothenic
acid
Folic acid
Biotin
Calcium
Magnesium
Potassium
Zinc
Copper
Selenium
Manganese
Iron
Iodine
Molybdenum
Chrome
Dietary fiber
Essential fatty
acids
Protein
Alkoxyglycerol
Aloe gel
Aloe whole leaf
Chitosan/chitooligosaccharide
Chlorella
CLA
Coenzyme Q10
Fructooligosaccharide
Gamma-linolenic acid
Ginseng
Glucosamine
L-theanine
Lecithin
Lutein
MSM
Mucopolysaccharide
N-acetylglucosamine
Octacosanol
Omega-3 fatty acids
Phosphatidylserine
Phytosterol/-ester
Plants containing chlorophyll
Probiotics
Red ginseng
Red yeast rice
Soy isoflavone
Soyprotein
Spirulina
Squalene
Banaba leaf extact
Evening primrose seed
extract
Ganodermalucidun fruit
body extracts
Garciniacambogia
extract
Ginko leaf extract
Green tea extracts
Guava leaf extract
Haematococcus extract
Japanese apricot extract
Milk thistle extract
Propolis extracts
Saw palmetto extract
Functional fiber:
Gua gum/hydrolyzates
Glucomannan
Indigestible
maltodextrin
Oat fiber
Soy fiber
Tree ear
Wheat fiber
Barley fiber
Arabic gum
Corn bran
Inulin
Psyllium husk
Polydextrose
Fenugreek seed
(28) (55)
Regulation on approval of functional
ingredient for HFF (Product-specific type)
functional ingredients other than what is listed in the HFF Code need to
be approved for health claims individually
Data needed to apply for a product to be
considered as HFF (Product-specific type)
• Hx of safe use
• Manufacturing processes
• Recommended intake
• Toxicological data
• Clinical data
• Nutritional evaluation data
• Bioavailability data
Soy Isoflavone (Generic type)
• Health claims: Help to maintain bone health
• Recommended intake: 24 ~ 27 mg/d as aglycone
soybean isoflavone
• Caution
– Infants, children, pregnant and lactating women
– Individuals who has an allergy to soybean
– Individuals who are sensitive to the estrogen
Isoflavone contents of common
soybean products in Korea
Korean J F&N, 2000
Isoflavone intake assessment in
South Korea
• Adolescents: 28.1mg/d
• Female college students: 33.8mg/d
• Middle-aged women: 24.4mg/d
– Pre-/post-menopausal women: 16.0mg/34.9mg/d
– Postmenopausal women: vegans/omnivores (33.9mg/
23.9mg/d)
• Intake level very close to that of Japanese
(25mg/d)
Soy isoflavone safety
• No safety data in Korea
• Current safe intake level for isoflavone:
30mg/d (aglycone) • Adopted the Japanese standards for isoflavone in
Special Foods for Health Purposes
• Health claims: helps eye health by maintaining
the density of macular pigments which can be
decreased by aging
• Daily intake amount: 10 ~ 20 mg as lutein
• Caution
– When taken in excessive amounts, it may turn the
skin yellow temporarily
Lutein (Generic type)
Efficacy reevaluation of ingredients
for HFF (generic type)
• 2012 Korea Ministry of Food & Drug
Safety reevaluation
– Recommended intake
• Omega-3 fatty acids: 0.5-2.0g/d
• Glucosamine: 1.5-2.0g/d
• Saw palmetto extracts: 70-115mg/d
• Coenzyme Q10: 90-100mg/d
Korea MFDS
Based on 2008 KNHANES data, Koreans consumed 1549
plant foods.
Collated flavonoid database on 1317 food items covering
85% of plant foods
Development of flavonoid database
for commonly consumed foods by
Koreans
Yang, et al., Korean J Nutr 2012
Flavan-3-ols intake associated with
metabolic syndrome in Korean
adults
• Daily intake: 30.0 mg/d (men) and 22.5 mg/d (women)
Low tea and red wine consumption in Korean adults may
be attributed to their low intakes of flavan-3-ols
• Estimated daily flavan-3-ols intakes of Australia (422
mg/d, black tea), Denmark (148 mg/d, fruits) and the
Netherlands (145mg/d, red wine). U.S. (158 mg/d) and
Spain (32 mg/d)
Yang, et al., Nutr Res Pract. 2012
Tomato extracts (Product-specific type)
• Health claim: Antioxidant (Health claims Grade
II)
• Recommended intake: [(all-trans)-lycopene]
5.7~15 mg/day
• Caution:
– Pregnant and lactating women
– Children
Establishing NRVs for
bioactive substances face
many challenges ahead!!
Challenges to provide intake
recommendations for bioactive
substances
• Bioactives content of plant
foods varies: sun, ripeness,
storage, preparation,
processing
• Bioavailability influenced by
chemical structures, baseline
diet, genetic makeup
• Very limited food database
• Difficult to assess usual
intake
• No solid health
outcomes/endpoints
• Usual intake of general
population << recommended
intake for efficacy
• Difficult enough to give a
recommendation for general
public living within one
country, may be impossible
to apply it to other
populations or those living in
other countries of a different
food culture
Gaine et al., Adv Nutr, 2013
Yeum, et al., APJCN 1999
Serum levels of lutein and
lycopene in South Korea
• Serum levels of healthy Korean adults
– Lutein: higher (30-40 μg/dL) than Western
populations (11-14 μg/dL). We consume a
significant amount of spinach and turnip greens
which are high in lutein content
– Lycopene: lower (7-11 μg/dL; tomato
consumption: 11.8g/person/day) than Spanish
(20-22 μg/dL, tomato consumption: 35.3
g/person/day) or US adults (NHANESIII 26.4 and
23.9 μg/dL for male and female, respectively)
Korean J Nutr 2009 J Geochem Explor 1997
Do we have enough evidence for
setting NRVs for bioactives?
CRN International Symposium Schlosshotel, Kornberg am Taunus, Germany November 1,
2013
• No DRIs established for bioactives
• Do have some data
– Intake assessment
– Health benefits
– Risk assessment
Basic types of data needed to inform
bioactive intake recommendations and
South Korea HFF
Type of data Specific application HFF (S. Korea)
Analytical Methods to characterize bioactive(s) V
Detect and quantify bioactive(s) in human sera and tissues V
Quantify bioactive(s) in the food supply
Quality control V
Preclinical In vivo data suggesting health benefit, bioavailability,
pharmacokinetics, risk assessment
V
In vitro data to establish mode of action, biologic plausibility V
Clinical Population intake patterns
Epidemiologic observation V
Intervention V
Biomarkers of exposure and efficacy V
Risk assessment V
Post-market surveillance V
Heber & Shao. IADSA, 2011
Setting NRVs for bioactives in South Korea
• Regulatory bodies for setting NRVs
– Korea Ministry of Food and Drug Safety
• Establish NRVs for labeling purposes: all processed foods
and Health Functional Foods
• Currently not considering NRVs for bioactives
• Revision of KDRIs is currently undergoing
– The Ministry of Health and Welfare is in charge of the
KDRIs
– Revised version due in 2015
• Establishing KDRIs for bioactives is not yet a subject of major
discussion
• An issue for a potential need for establishing DRIs for
bioactives was raised
Adequate intake
US Institute of Medicine’s Dietary Reference Intakes
AIs and ULS for Bioactives
Establishing Uls for bioactives
• Establishing Uls for bioactives should be
based on risk assessment
– Problems:
• no known NOAEL/LOAEL
– Use of WHO/FAO Highest observed intake
(HOI) approach
• Highest tested dose can be concluded as safe
Establishing Uls for bioactives
• For efficacy, the intake recommendation for
bioactives can be much higher (several fold ~
100 fold) than normally consumed by the
general population
• In some cases, need a more rigorous safety
data
• NRVs for bioactives need to be set at the level
which is not too close to the ULs
South Korea may be able to contribute to
establishing Uls for bioactives
• Postmarket surveillance system
– Adverse events (AE) reporting and signal generating system for
HFF is in operation from 2006 (Korea MFDS)
– On-line system for AE data collection
• Consumers: www.hfcc.or.kr
• Manufacturers: www.hfood.or.kr
• Healthcare professionals: hfoodi.kfda.go.kr
– Korea Integrated System for Signal Manipulation and Evaluation
of HFF:
• Integrated database for HFF Products, AE, Safety data
• WHO scale/Statistical analysis on cause-effect of AE
– Safety Evaluation Advisory Committee for HFF (27 members: MDs, Pharm Ds, epidemiology, statistics, consumer agency,
government officials, etc. )
CODEX NRVs
• Nutrient Reference Values (NRVs) are a set of
numerical values that are based on scientific data for
purposes of nutrition labelling and relevant claims.
• They comprise the following two types of NRVs: – Nutrient Reference Values - Requirements (NRVs-R) refer to NRVs
that are based on levels of nutrients associated with nutrient
requirements.
– Nutrient Reference Values - Noncommunicable Disease (NRVs-
NCD) refer to NRVs that are based on levels of nutrients associated
with the reduction in the risk of diet-related noncommunicable diseases
not including nutrient deficiency diseases or disorders.
GUIDELINES ON NUTRITION LABELLING, revised 2013
NCDS and Health Benefits of Bioactive Food Components
Trujillo, JADA 2006
Epigenetics
Hemostasis/thrombosis
Cell Oxidation
Positioning bioactives in the
Codex NRVs in the future
• Nutrient Reference Values -
Noncommunicable Disease (NRVs-NCD)
– Detrimental (?): macronutrients, sodium
– Beneficial (?): bioactives
The Science of Diet:
challenges in chemical biology
• Two challenges in chemical biology
– Protein chemical engineering studying protein dynamics: structure and function,
deciphering specific contributors of post-translational modifications
– The Science of diet: Disease prevention using natural products and their analogs
• Chemoprevention through dietary adjustments is attractive public
health strategy. But
• Need to move from phenomenological to mechanistic
• Skepticisms surrounding research in this area that lacked rigor and
molecular detail
• To exert a much greater impact on public health, key molecular
pathways need to be defined
Qualitative NRVs for Bioactives
Cole, BMC Biology 2013, 11:87
Thank you very much
for
your kind attention!
CRN International Symposium
Schlosshotel
Kornberg am Taunus
Germany
November 1, 2013