Vitamin

B6 requirements
oral contraceptive&
J. E. Lekiem,
Ph.D.,
and H. M Linkswiler,

R. R. Brown,
Ph.D.

ABSTRACT

Ph.D.,

Fifteen

and nine control

of women

using

2
D. P. Rose,

women

who

M.D.,

used

Ph.D.,

combined

estrogen-progestogen

oral

contraceptives

women

were given a vitamin

B6 -deficient
diet for 4 weeks and the same diet
supplemented with 0.8, 2.0, or 20.0 mg of pyridoxine
hydrochloride
for an additional
4 weeks.
At weekly
intervals
a variety of indices of vitamin B6 nutrition were measured to determine
rates of depletion
and repletion.
The tryptophan
load test (2.0 g) was significantly
different
in

Women
using estrogen-containing
oral contraceptives
excrete
elevated
amounts
of tryptophan metabolites
after
a tryptophan
load test
compared
with women
not taking
oral contraceptives
(1-3).
Elevated
levels
of 3-hydroxyanthranilic

acid

were

also

observed

in

basal

urines
from such subjects
(4). When pyridoxine
was administered
to such subjects
the excretion
of
tryptophan
metabolites
was
decreased
toward
normal
levels, but in some subjects
large
amounts
of the vitamin
may be required
(3).
These
data
have
been
widely
interpreted
as
indicating
that
the
use of oral
contraceptive
drugs

causes

an

increased

requirement

for

vitamin
B6, although
other
explanations
for the
altered
tryptophan
metabolism
may
be possible. To evaluate
the effect
of oral contraceptive usage
on the requirement
for vitamin
B6, a
variety
of indices
of vitamin
B6 nutrition
were
measured

control
became

to

determine

a diet
used to measure
became
physiological

Methods
The
cerning

the

rate

at

which

and oral contraceptive

using women
depleted
of this vitamin
while
ingesting
low in vitamin
B6. The same indices
were
the

repleted
levels

and

at which

these

From
the Division
of Clinical
Oncology,
University
of Wisconsin
Medical
School
and Department
of Nutritional
Sciences,
University
of Wisconsin
College
of Agricultural
and Life Sciences,
Madison,
Wisconsin
53706.
Supported
in part
by Wisconsin
College
of
Agricultural
and Life Sciences,
Contract
NIH, HICHD
72-2782
with the National
Institute
of Child Health
and Human
Development,
and Grant
No. CA-13302
from
the National
Cancer
Institute,
Public
Health
Service, Bethesda,
Maryland
20014.

subjects
with

materials

experimental
the selection

The American

rate

when
supplemented
of pyridoxine.

Journal

details
of these
studies
of subjects,
diets
used,
of Clinical

Nutrition

conand

28: MAY

indices
of vitamin
B6 nutrition
measured
were
reported
previously
(5). In brief,
9 healthy
control
women
(average
age 22.3 1.9 years), and 15 women
(23.2
3.1
years)
who had used oral contraceptive
agents
for at least 6 months
were given a diet that
contained
only 0.19 mg of pyridoxine
equivalents
per
day (6). Oral contraceptive
users started
the diet on
day 1 1 of a 21-day
pill sequence.
Control
subjects
started
14 days after onset of the previous
menses. For
the first 4 days, while baseline
studies were made, the
diet was supplemented
daily with 0.8 mg of pyridoxine
hydrochloride
(PN-HC1).
This supplement
was
then withdrawn
and both groups of subjects
consumed
only
the deficient
diet
for
28 days.
After
this
depletion
period,
subjects
were
supplemented
with
either
0.8, 2.0, or 20 mg/day
of PN-HCI
for another
28 days. Before release from the study,
subjects
were
supplemented
for a final
4 days
with
100 mg
PN-HC1/day.
During
the baseline
period,
and at
weekly
intervals
throughout
the study,
several indices
of vitamin
B6 nutrition
were measured
in each subject.
The indices
measured
included
urinary
tryptophan
metabolites
before
and after
a 2.0 g oral load of
L-tryptophan
(7, 8), urinary
cystathionine
after a load

1975,

pp. 535-541.

Printed

in U.S.A.

535

Downloaded from ajcn.nutrition.org by guest on September 15, 2015

the contraceptive
users.
However,
other
indices,
including
urinary
cystathionine
(3.0 g
L-methionine
load),
urinary
4-pyridoxic
acid, plasma phosphate,
and erythrocyte
alanine
and
aspartate
aminotransferases,
were
not
significantly
different.
Since
altered
tryptophan
metabolism
persisted
in contraceptive
users even when other indices of vitamin
B6 nutrition
were normal,
we suggest
that the use of oral contraceptives
specifically
affects
tryptophan
metabolism
by some means other than through
a vitamin
B6 deficiency.
Am. J. Clin. Nutr.
28: 535-541,
1975.

LEKLEM

536

El

AL.

of 3.0 g of L-methionine
(9, 10), urinary
4-pyridoxic
acid (5), plasma pyridoxal
phosphate
(5), and erythrocyte activities
of alanine
arninotransferase
and aspartate aminotransferase
(5). In order to study metabolism along the kynurenine
pathway
and to circumvent
any variations
in activity
of tryptophan
oxygenase,
loading
doses of L-kynurenine
sulfate (200 mg/dose)
were
given
initially,
at the
time
of maximum
deficiency,
and after repletion
with pyridoxine
for 4
weeks.

At comparable
times
of depletion
and at
equal
levels
of PN -HC1 supplementation,
the
mean
excretion
of tryptophan
metabolites
was
consistently
greater
than that of controls,
and
suggests
that
the requirement
for vitamin
B6
may
be slightly
greater
in oral contraceptive
users
than in controls.
However,
it should
be
pointed
out that
because
of large individual
variations
and
limited
numbers
of subjects,

Results

many
statistical

Measurement
lites

after

the

deficient

ceptive

of urinary

tryptophan

loading

diet

users

showed

excreted

and

xanthurenic

trol

subjects

prior

that

the

to

starting

oral

contra-

acid

These

differences

a 3.0

persisted

During

subjects

depletion,

excreted

metabolites,

increasingly

with

the

both

groups

large

amounts

oral

contraceptive

larger

amounts

these
differences
significance.
Details

g oral

Fig. 2. The
tryptophan

and increased
during
the period
of vitamin
B6
depletion.
This is summarized
in Fig. 1 which
shows
the yield
of tryptophan
metabolites
excreted.

of

of individual
tryptophan
lished elsewhere
(8).
The urinary
excretion

elevated
levels of kynure, 3-hydroxykynurenine
compared
with the con-

acetylkynurenine
(8).

metabo-

load

are

pub-

of cystathionine
L-methionine

1 levels
groups.

occurred

not
achieve
the excretion

metabolites

at

after

is shown

pattern
is different
metabolite
yield

tion
and
week
similar
in both
differences

of

do
of

in

from that of the

in that predeple-

of

cystathionine
However,

later

times,

were
apparent

and

during

of
of

users
I

excreting

consistently

controls.

Supplementation

0.8

of

control

the third
week
of repletion
had
stabilized
at essentially
values.
The
oral
contraceptive

the excretion
level
the
predepletion
users
supple-

the

excretion

with
0.8
a marked

mented
exhibited

tryptophan
of

tion)

higher

the

time.

same

contraceptive

than
The

mg

of

control

subjects

value
47

observed
and

use

was

the

to

normal

by

also

promptly

ments

of

2.0

values

considerably

values

for

these

levels.

which
which
with

within

1 to

contraceptive
by

PN-HC1,

lower
subjects,

Supplementation
with
20 mg/day
to control

of

in oral

tryptophan

ranges

oral

than

daily

with
the

users
suppleexcretion

predepletion

but

stifi

not

of

oral

contraceptive

promptly

restored

--8,

STUDY

-$4-------------+6,

-,

at

subjects

restored

decreased

mg

+8,4-

interrupted.

daily

0
-i
Ui

DLI OF

was

inflection

fmding
during

of the control

Excretion

U.
0

was

and

low

Ii

(predeple-

subjects

at day

PN-HC1

metabolism

weeks.

users
tion

the

after

C
U)
I
I0

of

excretion

starting

19 were
a consistent
with the 7-day
period

contraceptive

levels.

the

these

users

excretion

a0

-J

also

even

the

than

Supplementation

was

in

However,

for

markedly

at day
coincided

PN-HC1/day

reduction

higher

values

2.0

of

supplementation,

slightly

oral

mg

metabolites.

weeks
still

PN-HC1/day

subjects

within

reduced

of

the

dramatically
1 week,
and by

with

mg

than

at control
excre-

FIG. 1 . Yield of metabolites

excreted
after a 2.0 g
tryptophan
load by control
subjects
and oral contracaptive
users
(O.C.).
During
the first
4 days the
deficient
diet (-B6)
was supplemented
with 0.8 mg
pyridoxine
hydrochloride.
During
the second
+B6
period
the diets were supplemented
with the number
of milligrams
of pyridoxine
hydrochloride
indicated
in
the figure. The shaded
bars below the figure designate
the 7-day
period
when
oral contraceptive
use was
discontinued.
There
were 9 control
subjects
and 15
contraceptive
users.
During
the repletion
period
6
controls were supplemented
with 0.8 mg and 3 were
given
2.0 mg of pyridoxine
hydrochloride.
Of the oral
contraceptive
users, 5 were supplemented
with 0.8 mg,
6 with 2.0 mg, and 4 with 20 mg. The metabolites
included
in the yield value were kynurenine,
N-acetyl
kynurenine,
3-hydroxykynurenine,
anthraniic
acid
glucuronide,
o-aminohippuric
acid,
kynurenic
acid,
and xanthurenic
acid.

Downloaded from ajcn.nutrition.org by guest on September 15, 2015

nine

tryptophan

VITAMIN

B6 REQUIREMENTS

IN

ORAL
to

CONTRACEPTIVE

restore

either

PLP

values

group.

mg/day

to

and

appreciably

537

predepletion

levels

supplements

of

2.0

in

PLP

However,

for

levels

USERS

3 weeks

higher

resulted

than

starting

in

values

in

both

C.,J

(5).

groups

To evaluate
Ui
-J

ceptive

way

on

the

independent

of

Ui

z
z

metabolic

use

of

tryptophan

before

4I-

deficiency,

urenine,

and

at
WEEK
-B,

4-

+8,

FIG.

2. Urinary
excretion
of cystathionine
after a
load of L-methionine
in oral contraceptive
users
(O.C.)
and control
women.
During
the -B6
period
the diet contained
the equivalent
of 0.19 mg of
pyridoxine.
During
the +B6 period
the diet was
supplemented
daily
with
0.8,
2.0, or 20 mg of
pyridoxine
hydrochloride.
Cystathionine
was
measured
by
an amino
acid
analyzer
(modified
Beckman
model
1 20) using a modified
buffer gradient
system (9).

3.0 g oral

the

peak

individuals

and

because

of the

subjects,
these
differences
cance statistically.
Excretion
of urinary
creased

at

similar

rates

small

were

not

of

significant
contraceptives

but

metabolism

number

they
has

at

kynurenine

of
given

and

The

after

excretions
of
, acetylkyn-

are

shown

in Fig.

and 3-hydroxykynin the oral contra-

deficiency.
and

times
when

Excretions

xanthurenic

Because
of these

of

acid

were

of sizable
differences

indiwere

suggest
that
the use of oral
an
effect
on tryptophan

one

or

in addition

more

steps

to any

effects

beyond
they

may

have on tryptophan
oxygenase
activity.
Activity
of erythrocyte
alanine
aminotrans-

CONTROLS

the first 2 weeks

of repletion
with
PN-HC1
the
excretion
by oral contraceptive
users remained
above
that
of controls
at comparable
times.
Again,
because
of wide
variations
between

loads
were

acid

essentially
unchanged.
vidual variations,
none

OF STUDY
.#

mg

activity

group
than
in controls
at all three
and were
highest
in both
groups

acetylkynurenine

path-

the

deficiency,

of kynurenine
slightly
higher

were

ceptive
studied

at peak

contra-

0.8
2.0

#{149}

O.C.
0.8

#{149}#{163}-

2.0

0--0---

.7

.5

of

of signifi-

0
0

.3

>-

4-pyridoxic
in

both

acid
groups

-----

deof

subjects
(Fig.
3) and repletion
rates
during
supplementation
with PNHCl
were also quite
similar.
These
data
suggest
that
use of oral
contraceptives
has no measurable
effect
on
absorption,
utilization
or conversion
of pyridoxine
to 4-pyridoxic
acid (5).
Plasma
pyridoxal
phosphate
(PLP)
levels of
oral
contraceptive
users
were
slightly
lower
than
control
values
initially
and
remained
slightly
lower
throughout
the depletion
period
(Fig.
4). During
repletion
with
PN-HC1
no
differences
between
groups
were found.
Supplements
of 0.8 mg PN-HC1/day
were
not enough

-------

25

39

47

53

59

DAY OF STUDY
+8,

-B6

+8

FIG. 3. Urinary
excretion
of 4-pyridoxic
acid by
control
subjects
and oral contraceptive
users (O.C.).
During
the first 4 days, the deficient
diet (-B6)
was
supplemented
with
0.8 mg of PN#{149}HC1.During
the
-B6
period,
the basal
diet
containing
0.19
mg
equivalents
of pyridoxine
was not supplemented
with
B6. This diet was supplemented
in the +B6 period
with
0.8 or 2.0 mg PN.HC1/day.
The shaded
bars
indicate
the 7-day
period
each month
when
oral
contraceptive
use was interrupted.
Pyridoxic
acid was
assayed as previously
described
(7).

Downloaded from ajcn.nutrition.org by guest on September 15, 2015

urenine

200

xanthurenic

5. Excretions

on

monohydrate

, 3-hydroxykynurenine

kynurenine

effects

supplementation.

U)

C.,

any

sulfate

pyridoxine

of oral
metabolic

oxygenase,

L-kynurenine

effects

tryptophan

LEKLEM

538
-

PLP
CONTROLS

6.-

OC.

0.8.2.0I

a.

El

0.8

0---

20

0---

0
i0-

controls
groups

x0
6-

were
found
decreased

period.

the

4-

activity

of

In2

both

predepletion

points

were

of
the

of 0.8

mg

groups

after

100

of supplement
levels.

but not
supple-

had

levels.

with

This level
supernormal

activity
during

supplements

approximately
shown

and

increased
the activity
levels.
With
2.0-mg

supplementation
0.

initially
similarly

Daily

of PN-HC1
slowly
to predepletion
ments,

and
both

depletion
,

U)

a.

AL.

or

mg

risen

The

to
final

days

of

PNHC1/day.

resulted

in normal

or

4,

-J

a.
0

4---

---Be

WEEK

_L.-

OF STUDY

-64

-,

1- 4C as substrate.

HK--XR

YNB1

CONTROL

erythrocyte
preparations
were
after
fortification
in vitro with
levels
of PLP (Fig.
6). The percent

saturating
stimulation
progressed,

by PLP increased
and
did so to

as the

deficiency

extent
in
During
deficiency,
in vitro stimulation
by PLP did not
restore
activity
to predepletion
levels, suggesting that the decreased
activity
was due, in part,
to loss of apoenzyme.
Dietary
supplementation
with
PN- HC1 again
decreased
the
percent
stimulation
with no consistent
differences
between comparable
groups.
controls

says

and

Similar
were

oral

the

contraceptive

unstimulated
done

for

same

users.

and PLP-stimulated
aserythrocyte
aspartate

23

23

23
Period

23

23

of Study

FIG.
5. Excretion
of kynurenine
(KYN),
acetylkynurenine
(AK),
3-hydroxykynurenine
(HK),
and
xanthurenic acid (XA) by control
subjects
and oral
contraceptive
users (O.C.)
(given an oral load of 200
mg of L-kynurenine
sulfate)
prior
to vitamin
B6
depletion
(period
1), at the peak of deficiency
(period
2) and after repletion
with pyridoxine
(period
3). The
abbreviated
metabolic
pathway
serves to identity
the
metabolites
in each group
of bars. Metabolites
were
measured
as previously
described
(7).
ferase

(not

fortified

with

PLP

in

vitro)

at

weekly
intervals
throughout
the study
is shown
in Fig. 6. Details
were
reported
elsewhere
(5).
No differences
between
oral contraceptive
users

WEEK

FIG.

STUDY

The
upper
figure
shows
changes
in
alanine
aminotransferase
basal activity
(without
addition
of PLP in vitro) in controls
(CONT.)
and oral contraceptive
users (O.C.) during vitamin
B6
depletion
and repletion.
The daily
supplements
of
PN-HC1
(in mg) are shown on each curve. The lower
figure shows the percent
stimulation
observed
in the
activity
of this enzyme
when
saturated
in vitro by
added PLP.
erytkrocyte

6.

OF

Downloaded from ajcn.nutrition.org by guest on September 15, 2015

FIG. 4. Concentration
of plasma
pyridoxal
phosphate
(PLP) in controls
and oral contraceptive
users.
Footnotes
are the same as in Fig. 3. PLP was assayed
with
tyrosine
apodecarboxylase
using
L-tyrosine-

The
above
also assayed

VITAMIN

, and

aminotransferase

those
relative
ficiency

B6
the

REQUIREMENTS
findings

IN

paralleled

of

the
alanine
enzyme
although
the
decreases
induced
by vitamin
B6 dewere
not
as great.
Details
of these
have been
presented
elsewhere
(5).

studies

ORAL

CONTRACEPTIVE

which

time

control

The
oral

load

may

excretion

of tryptophan

contraceptive

test,

users,

was
loaded

after

significantly
controls

metabolites
the

by

different
prior

to

from

induction

of

subjects

slightly

that

deficiency.

lower

in oral

contraceptive

users,

not statistically
change
of these

different.
When
the
indices
were compared
dietary
depletion
of vitamin
B6 in both
the excretion
of tryptophan
metabolites
cystathionine
suggested
that
the oral
ceptive
group
might
be depleting
at a
rate

than

the

controls.

Other

were

rates of
during
groups,
and
contraslightly
indices,

including
4-pyridoxic
acid excretion,
plasma
Ply,
and
erythrocyte
aminotransferases
changed
at virtually
the same
rate in both
groups
during
depletion
and reached
the same
nadir at the time of maximum
deficiency.
Supplementation
with
pyridoxine
(0.8
mg/day)
resulted
in very
similar
restoration
rates

of plasma

PLP,

erythrocyte

alanine

transferase
and
ever, correction

urinary
4-pyridoxic
of urinary
excretion

thionine

tryptophan

and

However,

2.0

was

values

after

metabolites
was stifi

supplementation

by
elevated

the

oral
above

with

2.0

contracontrol

mg,

have

studies

(12,

13)

conjugates

effect
that

affect

the

altered

in

or steroid

activity

of

the

tryptophan

of

the

kynurenine

and
seems

it

the

Previous

steroids

the

kynureninase
Thus,

contraceptive
nal
effects

sug-

hormones

elsewhere

enzymes

pathway,
i.e.,
aminotransferase.

which

effects,

metabolism.

indicate

PLP-dependent

loads,

of contraceptive
an

can

effects

oxygenase

kynurenine

of
have

of this
enzyme
observations
in

kynurenine

usage

of

kynurenine
most
likely

metabolism

of oral

users
is the summation
of hormoon
tryptophan
oxygenase
and

kynureninase
general
vitamin

rather

than

the

production

B6 deficiency.

tion
is in agreement
with
Lumeng
et al. (14)
in

This

the

acid

and

plasma

compared

in

oral

contraceptive

They

found

report

a
by

urinary
levels

PLP

that

of

interpreta-

recent

which

thurenic

cases,

not

xanwere

users

and

xanthurenic

20-

to

acid

plasma

levels

decreased
oral

normal

dietary

information
of

range

PLP.
in

toward

had

Further,

PLY

the

use

continued
was

subnormal

during

contraceptive
with

reported
users in

plasma

subjects

but

usage.

first
tended

Since

presented,

the

contraceptive-induced

in

However,

changes

no

possiin diet

must
be considered.
Salkeld
et a!. (15) found
the
erythrocyte
aspartate
aminotransferase
stimulation
test to be abnormal
in almost
50%

of

oral

effect

contraceptive
of

duration

this
index.
4-pyridoxic

Rose
acid

users,
of

but

observed

contraceptive

et al. (16)
levels
and

about
the

19%
mean

controls.

of oral
4-pyridoxic

was

not

no

usage

found
increased

low

kynurenine-to-hydroxyanthranilate

group
at

of

low.

study,
they
contraceptive

34-year-age

of

biity

correspondingly

to the present
20% of oral

levels
months

weeks
restored
all indices
in both
groups
to
their respective
predepletion
levels and, in some
cases, to ultranormal
levels.
The detailed
data (8) show that the excretion
of tryptophan
ceptive
group

may

pathway

the

amino-

for

also

activity
present

small

the

activity
in rats

as adrenal-mediated

the
the

tryptophan

in contrast
that about

mg/day

that

most

slower
in the oral contraceptive
group,
although
not significantly
so. Similarly,
repletion rates between
groups
supplemented
with
2.0
mg of PNHCl
were
not
significantly
different.
The data clearly
indicate
that a daily
supplement
of 0.8 mg of PN-HC1
for 28 days is
not enough
to replete
either
controls
or oral
users.

gest

the

studies

excretion
was elevated
in most
contraceptive
users even
though
plasma
PlY
levels
were,

slightly

contraceptive

given

controls.

acid Howof cysta-

metabolites

on

spe-

of tryptophan
B6 levels. This

on
since

oral

relatively

of vitamin

as well

any

some

primarily

normal
the

on

urinary
hydroxyratios

contraceptive
acid

significantly

users
value

for

in

although
the

different

whole

from

Downloaded from ajcn.nutrition.org by guest on September 15, 2015

bypass

B6

direct

within
that

metabolism

oxygenase,

shown

This confirmed
previous
observations
of altered
tryptophan
metabolism
in oral contraceptive
users (1-3).
Other indices
of vitamin
B6 nutrition
measured
before
vitamm B6 depletion
were not clearly
different
in
oral contraceptive
users.
Thus,
urinary
cystathionine
and urinary
4-pyridoxic
acid were not
different
from
controls;
and plasma
PlY and
the
erythrocyte
aminotransferases,
while

vitamin

the

be

of estrogens
( 11).
However,

tryptophan

were

have

is independent

tryptophan

similarly

faster

on

539

suggests

may

effect

which

indices

This

contraceptives

effect
Discussion

all other

ranges.

cific

USERS

540

LEKLEM

The

activities

ferases,
are

of

particularly

considered

of

(17).

the

or

vitamin

with

the

but there
differences

and

contraceptive

oral

that

the

use

contraceptives

were no
between

in

study

in

vitamin

certain

subjects.

In

the

it
of

demonstrate

precise

clear-cut
between

contraceptive
vitamin
B6

users
nutrition

because

the limited
might
not

of

mental

subjects

induced

larger

was
the
to

differences
in vitamin
B6
control
subjects
and oral
when
a variety
of indices
of
were
measured.
Perhaps

number
of
have obtained

susceptible

vitamin

much

control

was
not
possible
(with
the
tryptophan
load
test)

requirements

, we

dietary

B6
present

to

contraceptive-

B6 deficiency.

number

of

subjects
experi-

Perhaps

subjects

with

some

of

a
the

minor
differences
would
have reached
significance.
However,
it is possible

statistical
to say that

the

se does

use

of

oral

significantly

contraceptives
or

quirement

for

women

using

subgroup

of

particularly
min B6

per

consistently
vitamin

these
women

increase

B6
agents.
may

abnormalities

re-

in the majority
of
However,
a small
well

exist

who

susceptible
to steroid-induced
deficiency,
and in these
women

metabolic

not

the

may

result

Fifteen

women

contraceptives

who

had

diet

deficient

equivalent

After
with

never

who
used
in

of

used
and

(19).

these

vitamin

0.19

estrogen-containing
nine

mg

control

women

agents were given a

B6 (containing
the
of

pyridoxine/day).

4 weeks, this diet was supplemented

daily
0.8,
2.0
or 20.0
mg of pyridoxine

hydrochloride

for

an

additional

weeks.

Initially,
and at weekly
intervals,
measurements
were
made
of several
indices
of vitamin
B6
nutrition,
including
urinary
tryptophan
metabolites
(before
L-tryptophan),

and
urinary

after
a 2.0
cystathionine

4-pyri-

and

after

oral
loads
of
initially,
at the

pyridoxine

differences

were

repleobserved

between
oral contraceptive
users and controls
in the above
measured
indices
with the exception of the tryptophan
load test, although
very
minor
differences
occurred
in several
of the
indices.
The data suggest
that the use of oral
contraceptives
may specifically
affect
tryptophan
metabolism
by some
means
other
than
through
a vitamin
B6 deficiency,
since altered
tryptophan
metabolism
persisted
even when
other
indices
of vitamin
B6 nutrition
were
normal.
The amount
of vitamin
B6 (as pyridoxine)
needed
to maintain
normal
levels
of
these
indices
(except
for tryptophan
metabolism) was between
0.8 and 2.0 mg/day.
The
data suggest
that if the use of oral contraceptives
type

of
does

the

effect

clinical

taking

the
alter

combined
estrogen-progestogen
the requirement
for vitamin

is a minor

significance

these

steroid

to

one
the

and
majority

preparations.

of

B6,

doubtful
of women

LI

We gratefully
acknowledge
the competent
and
dedicated
technical
assistance
of Joan Chesters,
Jane
Mueller,
Rekha
Anand,
Pat Stauber,
Heidi Kan, and
Richard
Arend
throughout
the conduct
of this study
and of Kay Deighton
and Suzi Pertzborn
for assistance
in preparation
of the manuscript.

are
vitaother

Summary

oral

200
mg
were
given

sulfate

significant

urinary

pyridoxal
phosphate,
and
and aspartate
aminotrans-

addition,

of deficiency,

No

oral

produce

which

maintained,
exception

of estrogen-containing

L-methionine),

plasma
alanine

load
(after

of
a

References
1. ROSE,
D. P. The influence
of oestrogens
on
tryptophan
metabolism
in man.
Chin. Sci. 31:
265, 1966.
2. PRICE,
J. M., M. J. THORNTON
AND L. M.
MUELLER.
Tryptophan
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Am.
J. Chin. Nutr. 20: 452, 1967.
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A. L., M. BRIN,
M. GORDON,
P.
DAVIS, M. MURPHY
AND H. SPIEGEL.
Vitamin
B6 metabolism
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I. Abnormal
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Am. J.
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S. A., D. P. ROSE
AND P. A. lOSELAND.
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H.
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In

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stimulation
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1 5% of contraceptive
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presented
above
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ample
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erythrocyte

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these

induction

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significant

subjects

B6

study

AL.

3.0 g load
doxic
acid,

thereof,

of

present

as expected

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consistent

aminotrans-

activation

indices

In

changed

control

PLY

reliable

nutrition
indices

erythrocyte
the

El

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A. R., AND B. J. MILES.
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203:
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Y. K., AND H. LINKSWILER.
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ORAL

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10.

B6