Supplementary Memorandum submitted by Professor H F
Woods, Chairman of the Committee on Toxicity of Chemicals in Food,
Consumer Products and the Environment (E60)
Since my appearance before the Select Committee on 19 May,
I have asked the Secretariat to provide the Select committee with
a copy of the working paper used by the Committee in its consideration
of the toxicity of Vitamin B6. As was explained by Mr Rooker when
he gave his evidence, this paper was marked "Commercial in
Confidence" because it contained information supplied by
industry on an "in confidence" basis. I understand that
the COT Secretariat are seeking permission from those who supplied
commercial information for this to be included in the paper copied
to the Select Committee.
I am pleased that this information is being made available,
since it is my firm belief that its wider availability would have
helped to prevent the misapprehension that the COT based its opinion
solely on the study by Dalton and Dalton. As you will see from
the working paper, we gave consideration to a large volume of
information, both on human and animal toxicity from Vitamin B6
before reaching our opinion on a level of intake that is without
risk of toxicity. Since all experts agree that high doses of Vitamin
B6 taken over long periods can cause damage to peripheral nerves,
the key issue we faced was to identify a level of intake that
can be taken over a lifetime by the whole of the population, including
those who may be more susceptible, without causing harmful effects.
It is important for the Select Committee to be aware of the following
factors which influenced our assessment:
— Much of the evidence is weak. This applies to
studies which failed to report harmful effects as well as the
studies which did, such as Dalton and Dalton. For example, many
of the "negative" studies were of short duration, involving
small numbers of cases and lacked validation of the doses of Vitamin
B6 taken. Many such reports are simply letters of case studies
that have not been subjected to scientific or medical review.
— The findings on animal studies were not used to
derive the safe limit, but we examined this evidence on both occasions
and we noted that extrapolation of these data gave a potential
safe level very close to that derived from the human data.
— We recognised methodological weaknesses in Dalton
and Dalton study, such as the lack of neurological confirmation
of neuropathy and the use of an internal control group. However,
this study has the advantage over many in that it has been subjected
to peer review, it included women and serum concentrations of
pyridoxal phosphate above the normal range which confirmed the
use of supplements, the group size was larger than other studies
and the duration of intake was sufficient to detect effects at
relatively low doses over a prolonged period.
— Many of the symptoms reported by Dalton and Dalton
were those observed at higher doses by Schaumburg but, since patients
were taking much lower doses for a far longer period, one would
not necessarily expect to see exactly the same syndrome.
— Two particular aspects of Dalton and Dalton are
important: (i) the evidence that duration of dosage is important
in the development of Vitamin B6 toxicity and (ii) the recurrence
of symptoms when Vitamin B6 intake was restarted. This was reported
to occur when Vitamin B6 was retaken at 50 mg per day in at least
three patients.
— Where evidence is weak, we adopt an approach that
is cautious but, we believe responsible for products sold freely
to the general public such as foods. This is often the case in
issues considered by the COT. For this reason and those outlined
above, we considered it would be remiss to ignore the evidence
from Dalton and Dalton which is consistent with that seen in animals
and at higher doses in humans.
— Where there is uncertainty in the precise safety
levels, it is usual practice for the burden of proof to rest with
industry to supply appropriate studies conducted to modern standards.
Although much anecdotal and unpublished information has been submitted,
we have not received adequate scientific studies of long term
supplementation of Vitamin B6 in humans to change our opinion
based on the available evidence.
I trust this is helpful in clarifying the approach taken
and the reasons why we did not dismiss all of the information
contained within the Dalton and Dalton study. I should note that,
although the consideration by other expert Advisory Committees
did not influence our thinking in any way, it would appear that
the views of the NAS are out of step with those taken by similar
respected groups in Europe.
Finally, I would like to reassure members of the Agriculture
Committee that the procedures we have followed in producing this
opinion are in line with those set out in "The Use of Scientific
Advice in Policy Making" published by the Office of Science
and Technology in March 1997.
26 May 1998
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