Memorandum submitted by Dr Derek Shrimpton
(E28)
I am writing as an independent consultant in
nutrition and food science. One of my clients is the Council for
Responsible Nutrition (CRN), whose members account for more than
90 per cent of the nutritional supplements manufactured in the
UK. I enclose a copy of my CV for your reference [not printed].
The proposal of the Government to limit the
free sale of vitamin B6 to units of 10 mg or less is not only
scientifically surprising but potentially harmful to many women,
possibly as many as one million in the UK.
The drive in nutritional science is towards
identifying patterns of eating which will result in good health,
not merely the elimination of deficiency diseases. The Government
recommendations to women considering pregnancy to consume substantially
more folic acid than that recommended as an RDA (Recommended Daily
Allowance) is an example of this.
In the case of vitamin B6 there are three levels
of use. None has been associated with any problem.
The first is to prevent deficiency disease and
is about 2 mg daily.
The second, more recently recognised, relates
to improving the condition of the heart and is about 6 mg daily.
The third relates to preventing undesirable
mood swings associated with Premenstrual Tension (PMT) and is
between 50 mg and 200 mg for a few days during each menstrual
cycle. It is estimated that one million women in the UK are in
this category.
The Government's advisors were thus asked to
make recommendations to eliminate a problem which did not and
does not exist. It is hardly surprising that the scientific literature
was less than helpful since there has been no case to study.
The difficulties facing the advisors are illustrated
in the following analysis of the papers that have been reported
as being the basis of their recommendations. Cohort studies are
those in which a group is observed over a period of time. Case
controlled studies are those relating to single subjects.
AN ANALYSIS OF PAPERS RELATING TO B6 BY DAILY
INTAKE AND SCIENTIFIC METHOD
|
Daily intake
(mg)
| Cohort
Studies
% | Case
Controlled
%
| Animal
Studies
% | Reviews
%
| Total
% |
|
| 0-10 | 2.5 | 2.5
| 0 | 0 | 5 |
| 11-49 | 0 | 0 |
0 | 1 | 1 |
| 50-99 | 4.5 | 3
| 0 | 2.5 | 10 |
| 100-199 | 8(1) | 2.5(1)
| 4 | 2.5 | 17(2)
|
| 200-500 | 8 | 0(2.5)
| 0 | 3(2.5) | 11(5)
|
| (500 | 1 | 0(12)
| 0(20) | 4(12) | 5(44) |
| Total | 24(1) | 8(15.5) | 4(20) | 13(14.5)
| 49(51) |
|
In this table the number in brackets refer to papers in which
a reversible sensory neuropathy (usually tingling in the fingers)
was reported. In all cases it disappeared when the vitamin B6
was withdrawn. The two per cent occurring between daily intakes
of 100 mg and 199 mg relates to two papers. One (1) was criticised
at publication and its observations have never been repeated.
The other (2) related to a single patient whose consumption was
not known for certain. Again the observations were not repeated.
Apart from these two papers, none has reported adverse effects
at daily intakes of 200 mg or less.
The scientific literature strongly supports the observations
first published in 1983 that daily intakes in excess of 500 mg
daily, and particularly in amounts of 2,000 mg to 3,000 mg are
associated with adverse effects which are usually described as
peripheral neuropathy. In this respect vitamin B6 behaves in a
manner common to most nutrients—in appropriate amounts they
are beneficial; in excess they can be harmful. A well known example
is salt: it is essential, but in excess it is toxic.
NEW INFORMATION
Since the report of the government's advisors (COT &
FAC), research scientists in the UK and in North America have
studied the very extensive literature relating to vitamin B6.
The subsequent publications have demonstrated that:
In many of the research reports considered by the government's
advisors, inadequate attention was given to the placebo effect
(3). A positive response by up to 10 per cent of a test group
can be expected from the consumption of a placebo.
The observations reported by the Daltons were not the result
of an excess of vitamin B6 (4). The clinical sequence was completely
different and therefore had another cause.
An analysis of 32 research studies with animals—dogs,
pigs, rats and mice—demonstrated that the use of a factor
of 100 to arrive at a safety factor for humans was inappropriate
(5). So large a factor is correctly used when little or nothing
is known of either the mechanism of the adverse effect or of the
extent to which the test animal is similar in its response to
the human. In the case of the vitamin B6 studies with animals
much is known of the mechanism of causing adverse effects at high
doses and in eight of the studies dogs were used whose response
is similar to that of humans.
RECOMMENDATION OF
THE US ACADEMY
OF SCIENCE,
7 APRIL 1998
Most recently a multi-disciplinary committee of the American
Academy of Science (6) has analysed the research literature relating
to vitamin B6 and has concluded that a satisfactory upper level
for its recommended use as a nutrient, particularly in the context
of PMT, is 100 mg daily.
This recommendation is adequate for the improvement of the
quality of life in the menstrual cycle—50 mg is the minimum
effective intake—and is sufficient to allow for individual
variation within a population in respect of response both to efficacy
and to excess.
CONCLUSION
The exhaustive studies of vitamin B6 made since the report
of the Government's advisors gives strong cause to revise the
proposed regulation.
There are two options for the Government to consider for
revision:
To accept the upper safe level of 200 mg for daily consumption
during the disturbing phase of the monthly menstrual cycle as
practised by consumers and provided by all members of the UK industry
through their requirement to abide by the industry's code of Good
Manufacturing Practice (7).
Or to accept the standard of the US academy of science of
an upper safe level of 100 mg made in the context of a wide ranging
review of safety issues in an international context.
15 April 1998
REFERENCES
(1) Dalton K & Dalton MJT, 1987. Characteristics
of pyridoxine overdose neuropathy syndrome. Acta Neurologica
Scandinavica 76, 8-11.
(2) Parry GJ & Bredeson DE, 1985. Sensory neuropathy
with low dose pyridoxine. Neurology 35, 1466-1468.
(3) McLean A, 1997. Risk assessment for B6 preparations
in: Vitamin B6: New Data—New Perspectives, pp 5-10,
CRN, Thames Ditton.
(4) Bernstein A, 1997. Objective measurements for peripheral
neuropathy in: Vitamin B6: New Data—New Perspectives,
pp 1-21 & 61-64; CRN, Thames Ditton.
(5) Munro I C, 1997. Predicting safety for humans from
animal studies in: Vitamin B6: New Data—New Perspectives,
pp 11-16 & 58-60; CRN, Thames Ditton.
(6) Food and Nutrition Board 1998. Dietary reference
intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin
B12, pantothenic acid, biotin and choline. Food and Nutrition
Board, Institute of Medicine, National Academy Press, Washington
D.C. (chairman of sub-committee on upper reference levels of nutrients—Munro
IC).
(7) CRN 1997. Guidelines for good manufacturing practice
for manufacturers of food supplements. CRN. Thames Ditton.
NOTES
Professor André McLean, University College London
Medical School, Centre for Clinical Pharmacology, Therapeutics
and Toxicology. Professor of Toxicology, University College, London.
Honorary Consultant in Toxicology, UCL Hospitals NHS Trust.
Dr Ian C Munro, Cantox Inc, Ontario, Canada. Director, Bureau
of Chemical Safety, Health and Welfare, Canada. Director General,
Food Directorate, Health Protection Branch.
Dr Allan Bernstein, Kaiser Permanente, California. President
of Medical Staff, Kaiser Foundation Hospital, Santa Rosa, California.
Co-Chief of Neurology, Permanente Medical Group, Santa Rosa, California.
Associate Professor of Clinical Neurology, School of Medicine,
University of California, Davis Campus, California.
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