Supplementary Memorandum Submitted by the Chairman,
Committee on Toxicity of Chemicals in Food, Consumer Products
and the Environment (E50)
STATEMENT OF PRELIMINARY OBSERVATIONS ON THE NAS REPORT
ON A TOLERABLE UPPER INTAKE LEVEL FOR VITAMIN B6
PURPOSE
This note is intended to record the outcome of our preliminary
consideration of a National Academy of Sciences (NAS) report on
B vitamins. We were asked to give an initial consideration of
the methods used and the recommendations for a Tolerable Upper
Intake Level of vitamin B6 in the NAS report in order to inform
the Chairman of the COT in advance of his appearance before the
House of Commons Select Committee on Agriculture Inquiry into
vitamin B6.
INTRODUCTION
The US National Academy of Sciences' Institute of Medicine
are publishing a report which establishes a set of Dietary Reference
Intakes for the B vitamins. The primary aim of this work was to
consider the requirements of B vitamins necessary to maintain
health. A Subcommittee on Upper Reference Levels of Nutrients
(UL Subcommittee) considered the evidence and advised on the adverse
effects of high intakes of B vitamins. The scope of the NAS report
was therefore much wider than the work of the COT which has reviewed
the toxicity of vitamin B6 on two occasions.
METHODOLOGY
We have been provided with the appropriate sections of a
pre-publication, uncorrected proof version of the NAS report.
Our own statement on the toxicity of vitamin B6 has been publicly
available since July 1997.
Both the NAS and ourselves have based advice on reviews of
the available literature on the safety of vitamin B6. Since a
wholly adequate study of the safety of high dose supplementation
of vitamin B6 in healthy individuals is not available, both assessments
have been made on a series of clinical studies and experimental
observations from which a tolerable or safe intake level has been
derived.
In our assessment, the Lowest Observed Adverse Effect Level
of vitamin B6 in humans was identified as a daily dose of 50 mg,
to which we applied an uncertainty factor of five to reach a recommended
maximum daily intake from dietary supplements of 10 mg. The NAS
considered that the No Observed Adverse Effect Level of vitamin
B6 was 200 mg, to which they applied an uncertainty factor of
two to derive a Tolerable Upper Intake Level of 100 mg.
CONCLUSIONS
As a result of our preliminary consideration of the NAS report
on vitamin B6 our conclusions are:
(i) We note the observation that there is no established
benefit for healthy individuals if they consume nutrient intakes
above the Recommended Daily Allowance or Adequate Intake;
(ii) We agree with the observation that, like all
chemical agents, nutrients can produce adverse health effects
if intakes are excessive and that there may be risks for subpopulations
with extreme or distinct vulnerabilities;
(iii) We note that in deriving a Tolerable Upper
Intake Limit for the B vitamins a Risk Assessment Model was used
which employed smaller uncertainty factors than used for non-essential
chemicals. This was justified on the grounds that "the consumption
of balanced diets is consistent with the development and survival
of humankind over many millennia". However, this is inconsistent
with the observation made subsequently in the report that the
effects of nutrients in fortified foods or supplements may differ
from the effects of nutrients available in a balanced diet. It
also ignores the fact that dietary supplements may be taken at
levels far exceeding those available from a balanced diet. Moreover,
the low uncertainty factor of two would (according to the model)
be appropriate for high quality data, which are not available
for vitamin B6;
(iv) We note that the study of Dalton and Dalton,
which reported adverse effects at daily doses of 50 mg, was dismissed
on grounds of methodological weaknesses. In our assessment of
the toxicity of vitamin B6 we recognised these weaknesses but
considered it would be unwise to ignore this evidence in the light
of the supporting animal data; likewise, we also recognise weaknesses
in those reports which have been used by the NAS for the determination
of the No Observed Adverse Effect Level.
(v) We note that there are no wholly adequate studies
of the safety of high-dose dietary supplementation with vitamin
B6, and that there are limitations with many of the studies. Nevertheless,
we consider it important to weigh up all the evidence and to take
a responsible approach for a substance with well established toxicity
but a poorly defined long-term dose-response relationship. Against
this background, we would not wish to change our earlier advice
on vitamin B6.
19 May 1998
|
