Association of South East Asian Nations (ASEAN)

ANNEX X
ASEAN GENERAL PRINCIPLES FOR
ESTABLISHING MAXIMUM LEVELS OF
VITAMINS AND MINERALS IN HEALTH
SUPPLEMENTS

Disclaimer:

This document is provided for information purpose only and subject to changes, pending the
finalisation of the ASEAN Agreement on Regulatory Framework for Health Supplements. Official
references to this document can only be made once the said Agreement has been finalised.

Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

DOCUMENT INFORMATION
This version was adopted at 15th ASEAN TRADITIONAL MEDICINES AND HEALTH
SUPPLEMENTS SCIENTIFIC COMMITTEE MEETING (ATSC) 25-27 June 2013, Singapore and
endorsed at the 18th ACCSQ TRADITIONAL MEDICINES AND HEALTH SUPPLEMENTS
PRODUCT WORKING GROUP (TMHSPWG) MEETING 15-16 November 2012, Brunei
Darussalam.

History of adoption and endorsement

Version
TMHSPWG endorsement Reasons for revision
No. ATSC adoption date
date
5th ATSC Meeting
1 -
29 Jul 2009
Inclusion of the paragraph “The ASEAN MLs are not intended
to be used as the levels of vitamins and minerals in health
11th ATSC Meeting
2 supplements that would bring beneficial effects to the
27-28 Jun 2011
ASEAN populations ” under Purpose & the exclusion of
fluoride from the list of minerals under Scope
Addition of Clause 2f “Despite the establishment of the
ASEAN MLs of vitamins and minerals, Member States may
consider exemption in their countries under special
12th ATSC Meeting 16TH TMHSPWH Meeting circumstances such as national requirements based on
3
19-21 Sep 2011 17-18 Nov 2011 country exposure assessment/ consumption survey or
product type classification. Such exemption with reasons
should however be made known to the other Member
States” under Scope
Addition of Appendix 1on the established values of ASEAN
maximum levels of vitamins and minerals in health
supplements that includes explanatory notes on the
15th ATSC Meeting 18TH TMHSPWG Meeting
4 conditions of use of vitamin K, the reasons of the non-
25-27 Jun 2012 15-16 Nov 2012
establishment of maximum levels of Potassium and Fluoride
as well as the country specific maximum levels of certain
vitamins and minerals.

1 of 11 Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

CONTENTS
Purpose ..................................................................................................................................................... 3

Scope ....................................................................................................................................................... 3

Guiding principles .................................................................................................................................. 4

1. Principles for Establishing Upper Limit (UL) Based on WHO Model ...................................... 4

2. Principles for Establishing Maximum Level (ML) Based on ERNA Model ............................ 6

ASEAN Maximum Levels ........................................................................................................................ 7

Glossary .................................................................................................................................................... 8

Appendix 1 ASEAN Maximum Levels of Vitamins and Minerals in Health Supplements . 10

2 of 11 Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

PURPOSE
The main purpose of establishing maximum daily intake levels of vitamins and minerals in
health supplements for ASEAN (“ASEAN ML”) is to ensure manufacturers only include safe
levels of vitamins and minerals in their health supplement products so that the normal use
of the products under the instructions of use provided by the manufacturers will be safe for
the consumers. The ASEAN MLs are not intended to be used as the levels of vitamins and
minerals in health supplements that would bring beneficial effects to the ASEAN
populations.

SCOPE
The following vitamins and minerals widely found in health supplements may be
considered for the establishment of ASEAN ML:

Vitamins Minerals

Vitamin A (Retinol) Calcium

Vitamin D Potassium

Vitamin E Phosphorous

Vitamin K Magnesium

Vitamin C Boron

Vitamin B1 Chromium

Vitamin B2 Copper

Vitamin B6 Fluoride

Folic acid Iodine

Vitamin B12 Iron

Biotin Manganese

Nicotinic acid Molybdenum

Nicotinamide Selenium

Pantothenic acid Zinc

3 of 11 Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

Only one set of ASEAN ML should be developed for the normal healthy adult population.
As far as possible, the needs of specific population groups should be factored into the
setting of ASEAN ML. If this is not possible, the needs of these subgroups could be
addressed by a more targeted approach through labelling or by individual dietary advice
provided by qualified health professionals. ASEAN ML for children should be developed in
a more targeted approach after the development of the ASEAN ML for adults.

The establishment of ASEAN ML should consist of Risk Assessment and Risk Management.
The Risk Assessment component involves the derivation of upper limit (UL) of a nutrient
based on the WHO Model. The Risk Management component involves managing the risk
of population intake exceeding UL when deriving ASEAN ML based on the ERNA Model.

The WHO Model has limited applicability in the derivation of UL of a vitamin or mineral that
has no reported adverse effects. If there is no basis for an UL because there is no evidence
of adverse effects for that particular vitamin or mineral, the Highest Observed Intake (HOI),
as defined in the WHO Model, should be identified.

There is no scientific basis for the use of RDA/RDIs in establishing ULs. The RDA/RDI is a
measurement of nutritional adequacy and not a measurement of health risk due to excess
intake. When the maximum levels are set, due account may be taken of the reference
intake values of vitamins and minerals for the population as outlined in the ERNA Model.
This provision should not lead to setting of maximum levels that are solely based on
RDA/RDI.

Despite the establishment of the ASEAN MLs of vitamins and minerals, Members States may
consider exemption in their countries under special circumstances such as national
requirements based on country exposure assessment/ consumption survey or product
classification type. Such exemptions with reasons should however be made known to the
other Member States.

GUIDING PRINCIPLES

1. PRINCIPLES FOR ESTABLISHING UPPER LIMIT (UL) BASED ON WHO MODEL

1.1. The model for nutrient risk assessment developed by the Joint FAO/WHO
Technical Workshop on Nutrient Risk Assessment 20061 (“WHO Model”) should be

4 of 11 Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

used as the guiding principle in the development of UL. In this context,

consideration of existing reports by authoritative scientific bodies i.e. EFSA, EVM
and IOM (EFSA, 20062 ; EVM, 20033 ; IOM, 19974 ,19985 , 20006 , 20017 ) that had
incorporated some or all of the principles of the WHO Model in their nutrient risk
assessments would be informative to the development of the UL.

1.2. The UL should be derived by following the steps of quantifying UL outlined in the
WHO Model i.e. identifying the critical adverse effects of the nutrient, choosing
the decisive scientific data upon which LOAEL or NOAEL is based, deciding on
the value of UF to assign and finally calculating UL using the formula (NOAEL ÷ UF)
or (LOAEL ÷ UF). The following is a schematic representation of the steps taken
from Figure 4-3 in page 40 of WHO (2006).

1.3. For the purpose of accelerating the establishment of UL, the selection of
parameters to be used in the derivation of the UL, namely critical adverse effects,
decisive data, LOAEL or NOAEL and UF, can be based on the data already
established by EFSA, EVM and IOM and if necessary, adjusted by newly available
scientific data. The newly available scientific data should be obtained from
widely recognized, authoritative, established references which have been
published or peer reviewed.

1.4. UL should be derived from maximum supplement intake data wherever possible.
UL can also be derived from maximum total dietary intake data if there are no
relevant maximum supplement intake data. If food consumption data showed
that the contributions of a specific vitamin or mineral from food were a significant

5 of 11 Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

fraction of the UL, the food intake data should be deducted to calculate the
ASEAN ML for health supplements.

1.5. The rationale for the determination of each parameter used in the derivation of
UL for each vitamin and mineral should be scientifically sound and properly
documented. The tabulation of comparative data from EFSA, EVM and IOM and
the final set of data chosen for the derivation of UL accompanied by appropriate
justification/explanation in a table format for each vitamin and mineral is deemed
sufficient for this purpose.

2. PRINCIPLES FOR ESTABLISHING MAXIMUM LEVEL (ML) BASED ON ERNA

MODEL

2.1. The model for nutrient risk management developed by ERNA (“ERNA Model”)8
should be used as the guiding principle in the development of ASEAN ML.

2.2. Following the derivation of UL, the nutrients should be divided three groups
according to the risk of population intakes exceeding UL. Group A is for nutrients
that do not have reported adverse effects and there is no risk of excessive
population intakes causing human health problems. Whereas Group B and C are
for nutrients with reported adverse effects. Group B is for nutrients with a low risk
whereas Group C is for nutrients with a potential risk of excessive population
intakes causing human health problems.

2.3. PSI, which is a measurement of the safety margin between the maximum level
from supplementation and population intake from food of a particular nutrient,
should be used to assign nutrients to Group B or C. Nutrients with PSI of more than
1.5 (i.e. higher safety margin) are assigned to Group B and those with PSI of equal
or less than 1.5 (i.e. lower safety margin) are assigned to Group C.

Risk of Excessive Intakes

Risk Categorization
Adverse Effects PSI Causing Human Health
of Nutrients
Problems
None reported Group A - None
Group B > 1.5 Low
Reported
Group C <= 1.5 Potential

6 of 11 Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

The following formula should be used for the calculation of PSI of nutrients with
reported adverse effects.

PSI = (UL – MHI) ÷ RLV

To enable the calculation of PSI, the MHI and the RLV of these nutrients must be
established. MHI should refer to the mean of highest intakes of a nutrient from
foods (e.g. at 95 or 97.5 percentile) whereas RLV should refer to the labeling RDA
of that nutrient which is being used as a surrogate of the desired population
intake. Appropriate foreign MHI or RLV values should be considered in the
absence of credible data from ASEAN countries. All MHI and RLV values should be
reviewed periodically.

2.4. The following formulas may be used to establish ASEAN ML:

ASEAN ML of Group A nutrients = HOI ÷ UF – MHI

ASEAN ML of Group B nutrients = UL – MHI

ASEAN ML of Group C nutrients = UL – MHI

However, appropriate risk management measures proportionate to the relative

risk associated with each risk group of nutrients should be taken when using these
formulas to establish the respective ASEAN ML.

For nutrients that have no established hazards at high intakes, their maximum
intake levels with sufficient evidence of safety (observed safe level) may be used
to establish ASEAN ML.

Special effort must be taken in the derivation of the ASEAN ML for Group C
nutrients to minimize the chance of exceeding UL. In addition, appropriate risk
communication can be instituted for certain Group C nutrients on a case-by-case
basis if necessary.

ASEAN MAXIMUM LEVELS

The list of established ASEAN maximum levels of vitamins and minerals appears as
Appendix 1.

7 of 11 Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

GLOSSARY
EFSA European Food Safety Authority (European Union)

ERNA European Responsible Nutrition Alliance

EVM Expert Group on Vitamins and Minerals (United Kingdom)

FAO Food and Agriculture Organization of the United Nations

HOI Highest Observed Intake

IOM Institute of Medicine, National Academies of Science (United States of

America and Canada)

LOAEL Lowest Observed Adverse Effect Level

MHI Mean Highest Intakes (the mean of highest intakes of a nutrient from foods
at 95 or 97.5 percentile)

ML Maximum Level (a risk management value for the highest safe intake level
of Vitamins and Minerals in Health Supplements in a population)

NOAEL No Observed Adverse Effect Level

PSI Population Safety Index

RDA Recommended Dietary Allowance

RDI Recommended Dietary Intake

RLV Reference Labelling Value

UF Uncertainty Factor

UL Upper Limit (a risk assessment value for no adverse effects)

WHO World Health Organization

8 of 11 Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

REFERENCES
1. Joint FAO/WHO Technical Workshop on Nutrient Risk Assessment. A model for
establishing upper levels of intake for nutrients and related substances. Geneva: World
Health Organization, 2006.

2. Scientific Committee on Food and Scientific Panel on Dietetic Products, Nutrition and
Allergies. Tolerable Upper Intake Levels for Vitamins and Minerals. Parma: European
Food Safety Authority, 2006.

3. Expert Group on Vitamins and Minerals. Safe Upper Levels for Vitamins and Minerals.
London: Food Standards Agency, 2003.

4. Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium,

Vitamin D, and Fluoride. Washington, DC: The National Academies Press, 1997.

5. Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin
B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: The
National Academies Press, 1998

6. Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and
Carotenoids. Washington, DC: The National Academies Press, 2000.

7. Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron,
Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium,
and Zinc. Washington, DC: The National Academies Press, 2001.

8. Scientific Advisors to ERNA and EHPM. Vitamin and mineral supplements: a risk
management model. Brussels: European Responsible Nutrition Alliance, 2004.

9 of 11 Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

Appendix 1 ASEAN MAXIMUM LEVELS OF VITAMINS AND

MINERALS IN HEALTH SUPPLEMENTS
Vitamin A (Retinol) 1.5 mg/day (5000 IU/day)

Vitamin D 0.025 mg/day (1000 IU/day)

Vitamin E 536 mg/day (800 IU/day)
Vitamin K 0.12 mg/day

Vitamin C 1000 mg/day

Vitamin B1 100 mg/day

Vitamin B2 40 mg/day

Vitamin B6 100 mg/day

Folic acid 0.9 mg/day

Vitamin B12 0.6 mg/day

Biotin 0.9 mg/day

Nicotinic acid 15 mg/day

Nicotinamide 450 mg/day

Pantothenic acid 200 mg/day

Calcium 1200 mg/day

Phosphorous 800 mg/day

Magnesium 350 mg/day

Boron 6.4 mg/day

Chromium 0.5 mg/day

Copper 2 mg/day

Iodine 0.15 mg/day

Iron 15 mg/day

Manganese 3.5 mg/day

Molybdenum 0.36 mg/day

Selenium 0.2 mg/day

Zinc 15 mg/day

10 of 11 Version 4.0
 ASEAN General Principles for Establishing Maximum Levels of
Vitamins and Minerals in Health Supplements

Notes:

1. The conditions of use of Vitamin K are as follows:

Application: For use in oral dosage form of multivitamin/mineral
preparations for adults and not as a single ingredient health
supplement
Vitamin K form: Only Vitamin K1 and/or Vitamin K2
Cautionary statement: “Consult a health care practitioner prior to use if you are on
anticoagulant therapy/taking blood thinners such as
warfarin”

2. The maximum levels of Potassium and Fluoride in health supplements are not
established. These minerals can be used in health supplements subject to the approval
of the national regulatory authority.

3. However, due to special circumstances such as national requirements based on

country exposure assessment/consumption survey or product classification type, the
established maximum levels of Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B6,
Folic acid, Nicotinamide, Calcium, Boron, Iodine, Iron, Molybdenum and Selenium are
not applicable to the Member States listed below. Some national maximum levels of
Member States are shown in parenthesis.

Vitamin A : Thailand(0.8 mg/day)

Vitamin D : Indonesia
Thailand(0.005 mg/day)
Vitamin E : Indonesia
Thailand(10 mg/day)
Vitamin K : Thailand(0.08 mg/day)
Vitamin B6 : Thailand(2 mg/day)
Folic acid : Thailand(0.2 mg/day)
Nicotinamide : Thailand(20 mg/day)
Calcium : Thailand(800 mg/day)
Boron : Thailand
Iodine : Malaysia(0.3 mg/day)
Thailand
Iron : Indonesia
Malaysia(20 mg/day*)
Molybdenum : Thailand(0.16 mg/day)
Selenium : Thailand(0.07 mg/day)

*For pre and antenatal use, as part of a multivitamin and mineral preparation, levels higher than
the 20 mg limit established for adults may be permitted at the discretion of the DCA.

11 of 11 Version 4.0