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*****************************************Risk Governance of Food Supplements

- The Case of Amino Acids -*****************************************

SRA-E Annual ConferenceKing’s College London

22 June 2010Michael D. ROGERS

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Food Risk Management* Evolutionary Changes *

In 1931 2000 people died in the UK from tuberculosis contracted

from milk. RM action: Pasteurisation of milk.

From 1993 to 2010 168 people died in the UK from vCJD disease caused by mad cow disease. RM action: EU imposed World-wide ban on UK beef exports from 1996-2006 (etc).

Regulation 1925/2006 on the addition of vitamins and minerals (etc) to foods “Excessive intakes of vitamins and minerals may result in adverse health effects and it is therefore necessary to set maximum amounts for them when they are added to foods”

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THE EU GENERAL FOOD LAW Regulation N° 178/2002 dated 28.1.2002

Demands “monitoring procedures for systematically searching for, collecting, collating and analysing

information and data with a view to the identification of emerging risks” (Article 34.1)

Where “the possibility of harmful effects on health is identified but scientific uncertainty persists” the

Precautionary Principle will apply (Article 7.1, 7.2)

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EU FOOD ADDITIONS (INGREDIENTS) LAW

Regulation N° 1925/2006 dated 20.12.2006

Primarily aimed at vitamins and minerals but other ingredients are to be considered later:

“if the possibility of harmful effects on health is identified but scientific uncertainty persists, the substance shall be

placed in Annex III, Part C” (Article 8.2(b))

“Substances under Community scrutiny”

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THE EU FOOD SUPPLEMENTS LAW Directive N° 2002/46 dated 10.6.2002

Primarily aimed at vitamins and minerals but other supplements are to be considered later (Article 4.8)

Maximum amounts of vitamins and minerals present in food supplements “upper safe levels ……. established by

scientific risk assessment” (Article 5.1(a))

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THE EU NUTRITION & HEALTH CLAIMS LAW

Regulation N° 1924/2006 dated 20.12.2006

There is a reversal of the “burden of proof” from the regulator to the producer so tendancy to deal first with

substances that are well evaluated in terms of safety (vitamins and minerals)

“In some cases, scientific risk assessment alone cannot provide all the information on which a risk management

decision should be based” (Preamble 29)

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Benefits and Risks

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Why are Amino Acids Important?

Amino acids are the oldest nutrients

20 amino acids provide minimal requirements for growth, nitrogen equilibrium, maintenance of host defences, neural and muscular functions, and gene expression regulation.

The catabolism of amino acids is an important source of energy.

The body is incapable of storing large amounts of amino acids and their homeostasis must be finely maintained.

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NB: The Harms associated with excess intake are generally much less serious than the harms associated with insufficient intake

General Shape of“Risk Curve”

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NOAEL: No Observed Adverse Effect LevelADI: Acceptable Daily IntakeSF: Safety Factor

Classical Risk Assessment

SF

NOAELADI

Usually 1/100

Animaltests

Pro

babi

lity

of

a P

arti

cula

r H

arm

Exposure to a Given Hazard

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*Int J Toxicology (2004) 23, 119-126 *Int J Toxicology (2004) 23, 113-118

Problems with the Classical RA Approach

Results from a standard risk assessment: Lysine NOAEL (male rat) = 3.4 g/kg/D* Resulting in an ADI (male human) = 2.4 g/D

BUT: The Dietary Intake of Lysine (Japan) = 5.27 g/D

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50 250 500 750 1000 1250 1500

0

1

2

3

4

5

6

7

Breakpoint = 555.8 mg/kg/dR2 = 0.895

Leucine Intake(mg/kg/d)

Leu

cin

e O

xid

atio

n

(F13

CO

2)

Leucine oxidation (F13CO2, µmol/kg/hr) in response to graded excess leucine intakes

Rajavel Elango, et alia, 2010 forthcoming “Determination of the Tolerable Upper Limit (UL) of Leucine Intake in Adult Humans” NOT FOR COPYING OR DISTRIBUTION

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Some Supplementation Benefits

Sports Use: Reduction in fatigue, Increase in endurance, Muscle development (Branched-Chain Amino Acids)

Medical Use: Trauma, Burns, Major Surgery - Reduction in mortality, etc. (Glutamine)

Third World Nutrition: Growth improvement in children, Improved Nutrition, Reduction in Diarrhoea, etc. (Lysine)

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The case of an essential amino acid, L-lysine (Lys)

Lys is the first limiting amino acid in most cereals. Addition of Lys to the basal diet improves nitrogen retention in small children, similarly to feeding them milk protein. Fortification of Lys alone increases the usability of flour protein ~ 2-times

Five double-blind trials were conducted by an NGO and Ajinomoto Co. in Asia and Africa, targeting protein status, growth, immune system, diarrhoea scores and mental health

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Results of the Lys fortification trials

Growth improvement in children

Improvement of nutritional protein status and immune status

Improvement in mental health (long-term anxiety, aggressiveness)

Drop in diarrhoea incidence (Bangladesh, Syria)

Smriga M et al., Proc. Natl. Acad. Sci USA 2004; 101: 8285-8288

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Identified Supplementation Harms

Amino Acids are a normal (and essential) component of human nutrition and no adverse health effects have been identified even at high intakes

ICAAS is funding research to identify effective intake upper limits (but homeostasis functions are very efficient)

Thus far identified “harms” resulting from high inputs are limited to disturbances in the digestive system (vomiting or diarrhoea)

Hence precautionary RM action would not be justified on either Proportionality or Cost-Benefit grounds

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Risk Managementof

Food Supplements

TheWAY FORWARD?

Better Risk Governance based onRisk-Benefit Analysis

Rather than Classical Risk Assessment?

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