COMMENTS
Since publication of our advice, I have been made aware of
a number of critical comments about the Committee's consideration
of vitamin B6. These criticisms, including those of Professor
Beckett and the "Vitamin B6 Scientific Task Group",
have been the subject of comment by members of the Committee.
We are clear that we have not seen any evidence that would convince
us that there is a need to alter our advice, and we have every
confidence that our conclusions are justified given the evidence
available to us.
I would like to make the following observations in response
to some specific criticisms summarised in italics below:
Vitamin B6 has been consumed at dosages up to 200 mg daily
by millions of people over several decades without any significant
hazards emerging.
The Committee would welcome the opportunity of evaluating
the scientific and clinical credibility of the data that gave
rise to this statement. Before undertaking our second review of
vitamin B6, the Committee sought information from those active
in marketing or recommending the use of vitamin B6 dietary supplements
as to the availability of such data; nothing was sent that would
support such a statement.
The Committee based its advice on a study by Dalton and Dalton
which has been discredited by other scientists
As noted above, although all relevant data were assessed,
it is the nature of risk assessment that the review of the totality
of data leads to the use of one or two critical studies for the
determination of safe doses. Overall it is clear that there is
an inverse relationship in animals and humans between intake and
time to adverse effects. The safety of long-term intake of low
doses of vitamin B6 has not been adequately studied. Nevertheless
we reviewed all the available data before producing our advice.
In humans, the lowest reported adverse effect level was 50
mg/day reported by Dalton and Dalton. In animals, the critical
study was the study in beagles reported by Phillips et al. The
Committee recognised the deficiencies in the Dalton and Dalton
study in its statement. In view of these limitations, this study
would not have been used by itself to derive a numerical recommended
intake, if this were the only information available. The data
of the Dalton and Dalton study are weak but consistent with an
inverse relationship between dose and duration to effect in humans
and serve to suggest a possible bottom limit to the relationship
between dose, duration and time to adverse effects. The Committee
would have been remiss to ignore the Dalton and Dalton study given
the other data on dose, duration and time to adverse effects in
both animals (dogs and rats) and humans.
The use of large safety factors is inappropriate, especially
for essential nutrients
Safety factors are used in regulatory toxicology to allow
for species differences and human variability. The use of safety
factors for xenobiotics but not for essential nutrients is an
unscientific distinction which is difficult to justify providing
that the resulting recommended intake is nutritionally adequate.
This is clearly the case for vitamin B6 since the recommended
maximum intake from dietary supplements is about seven times the
Reference Nutrient Intake (about 1.2 mg/day for women and 1.4
mg for men. The RNI is that amount of a nutrient that is enough
to meet the nutritional needs of almost all healthy people, even
those with high needs).
A factor of five was used to derive safe intake levels from
the level of 50 mg which has been reported to be harmful in humans.
It is reassuring that the standard safety factors applied to the
animal data lead to the derivation of a safe level that is similar
to that derived from human studies. Both the animal and the human
data suggest a dose of 10 mg is safe for the general population,
including susceptible groups such as the elderly, pregnant and
sick.
The COT advice ignored the benefits of vitamin B6 in treating
conditions such as the Pre-Menstrual Syndrome
The Committee on Toxicity advised on the safe use of vitamin
B6 as a dietary supplement, not on its medicinal use. Much of
the information supplied by interested parties that we considered
referred to the use of vitamin B6 to treat specific clinical conditions.
Assessment of the safety of medicines requires a balance between
risks and benefits—and this is a matter for the Committee
on Safety of Medicines. Our advice concerned the safe use of vitamin
B6 sold as a dietary supplement.
It is interesting to note that the authors who are cited
as providing evidence of no reported effects of vitamin B6 at
doses up to 200 mg/day are all presumably physicians who were
monitoring the progress and well-being of their patients. This
is exactly the situation which will obtain in the UK under the
new guidelines for General Sales List, Pharmacy, and Prescription
Only levels. Patients will not be prevented from obtaining daily
doses in excess of 10 mg but they will obtain these under supervision
of a pharmacist (up to 49 mg) or a doctor (above 50 mg). Given
the hazard/risk profile of high doses of vitamin B6 it is not
unreasonable to propose that treatment of a clinical condition
with a compound with well defined toxicity and a poorly defined
long-term dose-response relationship should be subject to medical
supervision.
Members may have been influenced by their interests with the
pharmaceutical companies
This is a highly spurious allegation, without foundation,
which I reject. As Chairman I have every confidence in the rigour
and independence of the advice of the committee.
8 April 1998
