Memorandum submitted by Consumers for
Health Choice (E24)
We warmly applaud the decision of your Committee
to hold an inquiry into the current issues of concern relating
to vitamin B6. We believe the Minister's decision to restrict
the free sale of this essential nutrient was based on erroneous
advice given to him by COT, which flies in the face of sound science.
Through your Committee, we are now able to present the facts which
will expose the flawed nature of COT's analysis—an opportunity
which we welcome and one that has been denied us since July 1997.
Consumers for Health Choice (CHC) is a non-profit
making international alliance of consumer organisations, practitioner
organisations, companies and prominent individuals. CHC has four
Directors, who work without remuneration. Formed in 1996, CHC
holds a data base of over 250,000 British supplement consumers,
who endorse CHC's actions in protecting the rights of consumers
to choose higher range food supplements that are scientifically
proven to be safe. Our supporters demand the right to take responsibility
for their own health without the use of pharmaceutical drugs,
and insist on the continued availability through specialist retail
outlets of higher dose vitamins, minerals and other safe supplements
of their choice.
Originally set up to monitor possible adverse
legislation regarding natural supplements from the EU, CHC has
successfully established itself as an organisation which is credible
to the institutions of the EU and one which is perceived legitimately
to represent the views of European consumers. CHC has been working
for almost two years to ensure that any proposal to harmonise
regulations governing the state of dietary food supplements in
the EU is carried out on the basis of as liberal an approach as
possible; a subsidiary objective has been to ensure that, if possible,
the currently liberal regimes applying in countries such as the
Netherlands and the UK should not become more restrictive as a
result of harmonisation.
CHC's purpose is to ensure that the voice of
the millions of consumers of higher range vitamin and mineral
supplements throughout Britain and the EU is heard by those framing
future regulations. Organisations supporting CHC in Britain, France,
Germany and Denmark have a membership of over 20 million individual
consumers.
The EU Commission's discussion paper on vitamins
and minerals was released in June 1997 and the first round of
consultations are complete. The Commission has just released a
second, more focused working paper and the next round of consultations
will start shortly. This second round of consultations will ultimately
lead to the preparation of the draft legislation on all vitamins
and minerals.
The vitamin B6 issue is purely a domestic
one and has nothing to do with the EU legislative process.
Nobody is quite certain WHY the British government
decided to place restrictions on the sale of vitamin B6 last July,
when DG III in Brussels had already released its discussion document
on ALL vitamins and minerals. What is certain, is that by taking
this action, the British government has sent a clear message to
Brussels that Britain has abandoned its position of supporting
upper safe levels. Without consulting nutritional experts and
without examining the sound science, the government is in fact
setting a dangerous precedent with vitamin B6 which could affect
all vitamins and minerals.
On 4th July 1997, the Food Advisory Committee
(FAC) issued a press release, endorsing the recommendation from
the Committee on Toxicity of Chemicals in Food, Consumer Products
and the Environment (COT), agreeing to advise Ministers that dietary
supplements should not provide a daily dose of more than 10 milligrams
of vitamin B6. In addition, the Committee advised that all dietary
supplements containing vitamin B6 should carry a warning against
over-use. The FAC noted that MAFF had recently circulated the
EU Discussion Paper on fortified foods and dietary supplements
and had initiated a formal consultation. However, the FAC stressed
that action on B6 was required on safety grounds and should not
be postponed until the outcome of the consultation was available.
As a result, on the same day, 4th July 1997,
the Minister, Mr Jeff Rooker announced publicly that he had asked
for legislation to be prepared to limit the free sale of vitamin
B6 to just 10 mg per day. Levels between 11-49 mg would be available
from behind the counter at a chemist, with doses above 50 mg available
on prescription only from a doctor.
The government say it is taking this action
on grounds of safety, because of possible nerve damage at low
levels. But world experts disagree. Professor Alan R Gaby, MD,
a top nutritional scientist from Bastyr University in Seattle,
USA, read the government's statements and has made this comment:
"I have studied this material most carefully
and as one who has reviewed all the published scientific literature
relating to vitamin B6 toxicity, I can say with confidence that
the analysis provided by the Minister is, quite simply, wrong."
Peer reviewed scientific literature strongly
upholds 200 mg per day as the safe level; no studies support such
a low level as 10 mg.
Vitamin B6 (pyridoxine) was discovered in 1934
by Professor Paul Gyorgy at the University of Pennsylvania, USA,
and has always been regarded as an extremely safe vitamin. B6,
a member of the vitamin B-complex, is water soluble, and therefore
cannot be stored in the body and new intake is required daily.
It is essential to life.
B6 is found in some of our most common foods
including bananas, yeast extract, oats, potatoes, chicken, fish,
liver, milk, green leaf vegetables, nuts and beer. Deficiency
of this essential nutrient can cause convulsions in infants, and
induce depression, anaemia and skin complaints in adults.
It is estimated that three million people in
the UK take a supplement containing vitamin B6 regularly. Many
people, especially women, have an increased need for vitamin B6
that cannot be satisfied through diet alone. The contraceptive
pill and Hormone Replacement Therapy are known to deplete the
body of vitamin B6, and these low levels may be related to the
mild depression many women experience. Alcohol drinkers and tobacco
smokers also have an increased need, as do those who live in towns
or anywhere the air is polluted. Those consuming a high protein
diet or taking some prescription drugs also benefit from additional
B6. Women's needs for B6 increase just before their monthly period,
it safely counteracts the effects of Pre-menstrual Syndrome (PMS),
and prevents morning sickness in pregnancy. A high percentage
of women with PMS problems have an inadequate uptake of B6, possibly
due to malabsorption or over-active oestrogen.
Known as the anti-stress vitamin, B6 is essential
for the production of serotonin, a brain chemical that affects
mood swings, behaviour and sleep patterns. Research has indicated
it can also help protect against carpel tunnel syndrome, (repetitive
strain injury), inflammation of the nerve as it passes through
the wrist—a common complaint in people who use a computer
keyboard daily.
Toxicity is low, so intakes up to 200 mg
per day are safe for long term use. However, the average amount
of vitamin B6 taken in supplement form by consumers is 100 mg
per day.
The COT claim to have examined more than 140
scientific papers. Their conclusion that B6 should be restricted
to just 10 mg is even more extraordinary because only one paper
claims to have seen B6 toxicity at low levels of 50 mg per day—the
Dalton and Dalton study—which has been heavily cricitised
by the scientific community for its methodological deficiencies.
Despite the wealth of scientific evidence available to them to
show B6 safety at 200 mg per day, COT have relied heavily on the
"Preliminary Communication" from Dr Dalton to support
their case.
The studies quoted by COT to support their recommendations
are:
DALTON K, DALTON
MJT. ACTA NEUROLOGICAL
SCANDINAVIA 1987; 76: 8-11.
Abstract
A retrospective study was made of 172 women
who had taken a B6 (pyridoxine) supplement for varying periods
up to nearly 5 years. 103 (60%) reported adverse effects, including
bone pains, muscle weakness and numbness. All were reversed when
the supplementary pyridoxine was withdrawn. In both groups, the
mean daily intake of pyridoxine was similar (116-117 mg), but
the group which experienced the adverse effects had been taking
pyridoxine for a period of 2.9 years, compared with 1.6 years
by the group that reported no side effects.
WATERSTONE
JA, GILLIGAN BS. MEDICAL
JOURNAL OF
AUSTRALIA, 1987;
146: 640-642.
Abstract
A 20 year old woman had been referred with neuropathy.
Included in her treatment had been a daily intake of 1,000 mg
of pyridoxine for 12 months. There was some improvement in her
condition after the pyridoxine treatment had been withdrawn.
BERGER AR, SCHAUMBURG
HH, SCHRODER C ET
AL. NEUROLOGY,
1984; 310: 986-987.
Abstract
A 34 year old woman, who had taken a multivitamin
supplement containing 200 mg of pyridoxine for three years with
no ill effects, increased the supplement of pyridoxine to 500
mg per day, with an additional weekly supplement of 300 mg. Neurological
dysfunction developed. This progressively declined when the pyridoxine
supplement was withdrawn.
ALBIN RL, ALBERS
JW ET AL.
NEUROLOGY, 1987;
37: 1720-1732.
Abstract
A husband (aged 33 years) and wife (aged 27
years) were given pyridoxine intravenously as an antidote to the
poisonous false morel mushroom (Gyromitra esculenia). During three
days, the man received 183,000 mg of pyridoxine and the woman
132,000 mg of pyridoxine. Both patients developed sensory neuropathy
after this massive overdosing.
PHILLIPS W, MILLS
JH, MUNRO IC ET
AL. TOXICAL
APPL PHARMACOL,
1978; 44: 323-333.
Subacute toxicity of pyridoxine hydrochloride
in the beagle dog.
Abstract
Neuropathological damage was observed in the
dogs after they had been fed on a diet including a very high level
of pyridoxine. The vitamin was included at a rate of 50 mg per
kilo of bodyweight and the effects were observed after 16 weeks
of continuous feeding. The level fed was the equivalent of 4,000
mg daily for a man weighing 80 kg (12½ stones).
Considering the huge number of scientific papers
available to them showing the safety of B6 (pyridoxine) at levels
of 200 mg, one must question why COT chose to mention just these
few, particularly as they involved so few people and were all
exceptional. In a further attempt to justify their recommendation,
COT stated that "We consider that the small number of individuals
involved and/or the short duration of administration may explain
the absence of signs of peripheral neuropathy in some studies".
It is important to examine the Dalton &
Dalton paper in detail, which we will do, as the COT and FAC have
placed so much importance on it. Part of the Dalton study was
first published as a letter to The Lancet on 18 May 1985. It was
immediately challenged by scientists Brush & Perry from the
Gynaecology Department of London's St. Thomas' Hospital.
DALTON K. THE
LANCET, 18 MAY
1985; 1168-1169.
Pyridoxine overdose in pre-menstrual syndrome.
Abstract
58 women were surveyed who had taken vitamins,
minerals and herbal supplements. The daily amount of pyridoxine
ranged from 50 mg to 300 mg. Serum B6 was above normal in 23 of
the 58 women and these were reported to have experienced neuropathic
symptoms.
BRUSH MG & PERRY
M. THE LANCET,
15 JUNE 1985; 1300.
Pyridoxine and the pre-menstrual syndrome.
Abstract
The authors emphasise the inappropriateness
of the RDA (recommended daily amount) in determining suitable
levels of consumption for nutrients which have valuable actions
at levels above the basal needs.
The authors comment that: "It is important
to note that after more than 10 years of widespread use of vitamin
B6, both in pre-menstrual tension and by women in general, there
are no other reports of adverse symptoms when doses of 200 mg
per day or less are used".
The authors draw attention to the inadequacies
of the experimental technique used by Dr Dalton and confirm their
own satisfactory experience of pyridoxine at daily intakes up
to 200 mg in many hundreds of women. The authors note that they
are aware of other reports of ". . . excellent acceptability
and safety".
The Doctors Dalton acknowledged the criticisms
of their experimental method expressed through correspondence
in The Lancet, in including the statement in their definitive
paper that ". . . there may have been inaccuracy in the patient's
recall of the exact dose and duration of B6 intake when the period
of ingestion exceeded five years".
The controversy over the validity of the Dalton
preliminary communication continues. Dalton reports adverse effects
at daily intakes of 100 mg or less. We believe Dalton is the only
person claiming to have seen toxicity at 50 mg or less and her
list of symptoms is not in keeping with any other research on
B6 toxicity.
We know of no other evidence to support limitation
to 10 mg per day and are appalled that the government would even
consider doing so based on a single, at best flawed, paper published
11 years ago.
The controversial communication (Dalton K. 1985)
in a letter to the editor of The Lancet, reported that
23 out of 58 women (40 per cent) being treated with pyridoxine
for pre-menstrual syndrome experienced sensory neuropathy (characterized
by the author as burning, shooting, tingling pains, parathesia
of limbs, clumsiness, ataxia, or perioral numbness). Dalton (1985)
reported that these patients were taking 50-300 mg of pyridoxine
per day "supplemented by a variety of multi-vitamin preparations"
(which would all have contained extra B6). Because of this, no
conclusions can be made with respect to the doses of pyridoxine
these women may actually have received.
Furthermore, no information is provided in this
communication as to the duration of treatment with pyridoxine
or the concomitant use of medications or herbal preparations.
It is not clear how many of the women interviewed in this communication
were included in a later publication by Dalton and Dalton (1987).
This case report has drawn much criticism because of the severe
methodological flaws in the study and the fact that the conclusions
conflict with the remainder of the extensive pyridoxine database.
Without reliable dosing information, no conclusions pertaining
to a safe exposure level for pyridoxine can be made on the basis
of this study.
In subsequent publication, (described by Dr
K Dalton as a "preliminary communication"), which may
have included patients from the earlier case-report (Dalton,
1985), Dalton and Dalton (1987) retrospectively studied
172 women attending a private practice specialising in pre-menstrual
syndrome. In this study, there were no direct clinical investigations
by trained neurologists to confirm the presence or absence of
peripheral neuropathy. Diagnosis was apparently performed by asking
of a list of subjective questions which prompted responses consistent
with the symptoms of peripheral neuropathy (ie, on the basis of
being "asked if they experienced altered sensations in their
limbs or skin, or if they had noticed muscle weakness or pains").
This methodology is seriously flawed. It provides leading
questions to subjects which would tend to bias results.
In the study, the women were divided into two
groups; those who complained of neurological symptoms (103 out
of 172 or 60 per cent) and those who did not (69 out of 172 or
40 per cent). All the women had elevated blood serum vitamin B6
levels. The lack of objective clinical neuro-physiological assessment
precludes the determination of a definitive diagnosis, especially
for sub-clinical effects. Moreover, there appeared to be no confirmation
of the actual doses of pyridoxine consumed by subjects in the
Dalton and Dalton (1987) study, nor did the authors take
into consideration the amount of pyridoxine consumed from other
sources such as multi-vitamin supplements. The weaknesses of the
study design and the lack of consistency of the results—with
the weight of evidence pertaining to the higher doses of pyridoxine,
makes it impossible to use these data to determine an upper safe
limit of exposure for pyridoxine.
In the Dalton communication, the reported doses
of pyridoxine were not different between the two groups; 117
92 mg per day (mean standard deviation) in the "neurotoxic"
group versus 116 66 mg per day in the "control"
group. However, the authors reported a statistically significant
difference between the duration of treatment; 2.9 1.9 years
(mean standard deviation) in the "neurotoxic"
group versus 1.6 2.1 years in the "control" group.
The biological significance of this statistical difference is
unclear.
Dalton and Dalton (1987) also report
that 21 women in the "neurotoxic" group were reportedly
taking under 50 mg of B6 per day, and that 39 women were taking
less than 100 mg per day. Even when considering the possible extended
duration of exposure of these women (ie, no woman in the "neurotoxic"
group had taken pyridoxine for less than six months), the data
as presented are inconsistent with the findings of more reliable
case reports and the pyridoxine data base as a whole. Of particular
concern in Dalton's work, is the discussion of one individual
who was reported to have experienced neurological symptoms at
a dose of50 mg per day. It must be noted that this woman had
reportedly been taking higher dose levels of pyridoxine for two
years before stopping.
After her symptoms subsided, this individual
reportedly began taking pyridoxine at the dose of 50 mg per day
for only three months before a return of the same neurological
symptoms. An important deficiency of this observation is that
there is indication that the re-challenge was done in a double
blinded fashion. Dalton and Dalton (1987) also mention
three women with subnormal serum B6 levels—two months after
stopping treatment (their previous intakes were not reported).
Upon being told to take doses of pyridoxine of 50 mg per day,
these same three women reportedly started experiencing neurological
symptoms within one month. Again, it is inappropriate to use
a single data point from a poorly designed subjective study, in
which the dosing information was inadequate and the diagnosis
unconfirmed, to base a decision regarding the potential upper
safe limit of exposure to pyridoxine.
Although the Committee on Toxicity stated
that it was aware that "the study by Dalton and Dalton has
some methodological deficiencies", nevertheless, they have
used this study to prop up an upper safe exposure limit of 10
mg per day—a limit that is not supported by the wealth of
scientific evidence nor, following critical review, by the actual
Dalton studies themselves.
THE DEFICIENCIES
OF THE
DALTON & DALTON
(1987) STUDY ARE
SO GREAT,
THEY PROHIBIT
THE USE
OF THE
FINDINGS IN
MAKING A
DECISION AS
TO THE
UPPER SAFE
INTAKE OF
PYRIDOXINE FOR
LONG TERM
USE
The lowest reported adverse effect level of
supplemented pyridoxine in animals is 50 mg per kilo of body weight
per day, reported in beagle dogs treated for an average of 107
days (Phillips et al, 1978). In this study, groups of four to
five female dogs were treated orally with pyridoxine HC1 in gelatine
capsules to provide doses of 0, 50 or 250 mg pyridoxine per kilo
of body weight per day, in addition to a nutritionally balanced
diet. Animals in the high dose group had to have the dose level
reduced to 200 mg per kilo of body weight per day within the first
week of dosing, as all five animals developed incoordination and
clumsiness. For animals in the high dose group that had the dose
reduced within the first week, the signs disappeared within the
following seven days. In four to five animals, these signs reappeared
40 days after the start of the study (the remaining dogs developed
these symptoms 75 days after starting treatment). No animals in
the low dose group (50 mg per kilo of body weight per day) demonstrated
any clinical manifestations of neurotoxicity despite the use of
battery neurological tests and assessments.
After 100-114 days of treatment, all animals
were necropsied and subject to a complete histological examination.
The low dose used in this animal study ie, 50
mg per kilo of body weight per day, would equate to a human dose
of 3,000 mg per day in a 60 kg (9½ stones) individual. Human
doses at this level have been clearly associated with pyridoxine
induced peripheral neuropathy. This observation is consistent
with the pyridoxine clinical database and is not consistent with
the COT conclusion that the upper safe level for long term use
is just 10 mg per day.
The COT used the results of this study to estimate
a safe human dose of pyridoxine, based upon the application of
a 300-fold safety factor (10-fold for the use of animal data,
10-fold for inter-individual human variation, plus an additional
three-fold for the use of a lowest adverse effect level).
There is no justification for the COT to
use a 300-fold safety factor. It has been suggested that COT "invented"
the 300-fold factor to arrive at the figure they wanted.
The probable safe dose in humans was calculated
by COT as approximately 0.17mg per kilo of body weight per day
ie, 50 mg per kilo of body weight per day—divided by 300.
This equates to a daily dose in a 60 kg individual of 10 mg, which
is not at all consistent with the human data.
Based on a critical analysis of all the available
human and animal data pertaining to the safety of pyridoxine,
nutritional scientists conclude that daily doses up to 100 mg
can be consumed without any risk of adverse health effects. There
is scientific basis for informing consumers that large doses of
pyridoxine, greater than 200 mg per day, may carry with them a
small risk during long term ingestion.
Many consumers who wrote to Mr Rooker expressing
their concern about the B6 restriction, were sent a letter that
included the statement "There have been reports under the
MCA's voluntary Yellow Card Adverse Drug Reaction reporting scheme
of adverse reactions associated with medicinal products containing
vitamin B6. Since 1964, there have been 649 reports of 1,181 spontaneously
generated adverse reactions associated with such products, of
which 16 were fatal. The majority of these were associated with
products containing a number of constituents, but 410 reactions
are associated with products containing only B6".
This statement was part of a written reply given
by the Lord Donoughue in response to a question from Lord Kitchener
PQ.691—23 July 1997. The reply was a carefully worded report
of information held on the data base of the MCA. To those who
are not completely familiar with the "yellow card" system,
the reply could be misleading and, unless it was studied with
care, the lay reader could conclude that vitamin B6 had been shown
to be the cause of death. This is not the case at all.
The "yellow card" system is a voluntary
procedure through which medical practitioners report their usage
of prescribed products, usually but not always, selecting for
report incidents which were or might have been injurious to the
patient and some, but not necessarily all, of the associated prescriptions.
It is also important to recognise that the report on the "yellow
card" is the amount prescribed—not the amount consumed.
They may or may not be identical.
Lord Donoughue reported 1,181 adverse reactions,
16 of which were fatal. None of the fatalities recorded vitamin
B6 as the cause of death. Many resulted from coronary and
circulatory disease and at least one was from TB. It was not stated
by Lord Donoughue if this patient had received Isoniazid, but
when this drug is used to treat TB it is customary to prescribe
vitamin B6 at 150 mg daily to overcome the neuropathy caused by
the inactivation of the vitamin within the body by the Isoniazid.
If this had been the case, its omission from the reply could have
been misleading.
No clinical examination has been published of
the 1,181 patients reported since 1964 (an average of 35 per year)
through the "yellow card" system. Placed in context,
the data reported by Lord Donoughue cannot be accepted as evidence,
either in support of the efficacy or vitamin B6, or as evidence
of potential danger from it. Neither can the data be used as a
record of the daily consumption or of the period of time for which
it was consumed.
Consumers for Health Choice welcomes the Government's
determination to restore public confidence in food safety policy.
We also endorse the Government view that such food safety policy
should be formulated on the basis of sound science and we note
that the Minister for Food Safety and his colleagues at the Department
of Health have set up the new Ad Hoc Expert Advisory Group to
consider the safety of all dietary supplements over the next 18
months. To know that the meetings of this Group will be open to
outside observers and that minutes will be published is a great
step forward.
Vitamin B6 is no exception. If there was a genuine
safety issue with this essential nutrient, CHC would be first
in line to encourage the Government to act—and to act quickly.
But that is not the case.
The Minister's decision has been taken on the
basis of flawed scientific advice. His proposals, which will set
the benchmark for all vitamins, should be abandoned completely
in view of the existing voluntary limit set by the British Health
Food Industry—and the current activities of DG III in Brussels
who will shortly announce draft legislation for all vitamins and
minerals. Perhaps the most sensible move, and one which would
be satisfactory to the majority, would be either to do nothing
for the time being and ask the new Ad Hoc Group to examine vitamin
B6 as a matter of priority, or to give statutory force to the
industry's existing science-based voluntary limit of 200 mg per
daily dose.
Thank you for allowing us to present our case.
Please don't hesitate to make contact if anything is unclear,
or you would like further information on any of the points raised.
15 April 1998
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