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 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.

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,

Downloaded from https://academic.oup.com/ajcn/article-abstract/28/5/535/4732916 by Washington University in St. Louis user on 09 April 2018

pp. 535-541.

Printed

in U.S.A.

535

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

nine

,

and

xanthurenic

trol

subjects

tryptophan 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

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

4

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-

levels.

Downloaded from https://academic.oup.com/ajcn/article-abstract/28/5/535/4732916 by Washington University in St. Louis user on 09 April 2018

2

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.

VITAMIN

B6 REQUIREMENTS

IN

ORAL to

CONTRACEPTIVE

restore

either

PLP

values

group.

mg/day

to

2

and

appreciably

537

predepletion

levels

supplements

of

2.0

in

PLP

However,

for

levels

USERS

3 weeks

higher

resulted

than

starting

in

values

in

I

both

C.,J

(5).

groups

To evaluate Ui -J

metabolic

ceptive use on way independent

0

of

Ui

z z

the

tryptophan

oxygenase,

L-kynurenine

0

before

I

4I-

sulfate

deficiency,

pyridoxine urenine,

4

and

urenine

at 3

WEEK -B,

4-

4

5

6

7

+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

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

acetylkynurenine

8

pathactivity

deficiency,

of kynurenine slightly higher

were

ceptive studied

2

at peak

xanthurenic

5. Excretions

z

contra-

200

, 3-hydroxykynurenine

kynurenine

of oral metabolic on the

monohydrate

supplementation.

U)

C.,

effects

tryptophan of any effects

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

-----

de-

groups

of

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

Downloaded from https://academic.oup.com/ajcn/article-abstract/28/5/535/4732916 by Washington University in St. Louis user on 09 April 2018

-------

-

9

25

3

-

i

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).

LEKLEM

538 -

1

PLP CONTROLS

6’.-

OC.

0.8.2.0’I

a.

El

0.8

0---

20

0---

and controls both groups

depletion ,

2

U)

0

a.

AL.

i0-

6-

0.

4-

the

Daily

of

4

In2

and

activity during

supplements

both

with

mg

mg

but not supple-

had

levels. 3 or

100

of supplement levels.

of the

of 0.8

activity 2.0-mg

groups

predepletion were after

supplementation

This level supernormal

initially similarly

increased the levels. With

activity

approximately points shown

x 0 0

period.

of PN-HC1 slowly to predepletion ments,

8

were found decreased

risen

to

The final 4 days of PNHC1/day.

resulted

in normal

or

4,

-J

a. 0

2

-

4---

3

WEEK

-

---Be

4

5

_L.-

L

7

8

OF STUDY

-

-

-64

i

6

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

saturating stimulation

-,

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-tyrosine1-’ 4C as substrate.

HK--XR

YNB1

The above also assayed

CONTROL

by

PLP

increased

and

controls

says

did

as the

and

Similar were

oral

so to 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. progressed,

contraceptive

unstimulated done

for

same

users.

and PLP-stimulated aserythrocyte aspartate

a

q

‘23

I

‘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

weekly in Fig.

intervals 6. Details

No

differences

fortified

with

PLP

throughout the were reported between

oral

in

vitro)

at

study is shown elsewhere (5).

contraceptive

users

Downloaded from https://academic.oup.com/ajcn/article-abstract/28/5/535/4732916 by Washington University in St. Louis user on 09 April 2018

2

3

WEEK

FIG.

5

STUDY

6

7

8

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.

4

OF

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 bypass

slightly

that

B6

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 slightly

tryptophan

and

users.

However,

2.0

values

after

metabolites was stifi

supplementation

by elevated

the

was

oral above

with

2.0

4

contracontrol

mg,

Downloaded from https://academic.oup.com/ajcn/article-abstract/28/5/535/4732916 by Washington University in St. Louis user on 09 April 2018

have

(12,

13)

that

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.

affect

PLP-dependent

loads,

effect

indicate

can

effects

of contraceptive an

of have

of this enzyme observations in

oxygenase

kynurenine

conjugates

activity in rats

kynurenine

usage

of

studies

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,

the

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

activity present

small

the

the

studies

as adrenal-mediated

the the

tryptophan

not

in contrast that about

amino-

for

also

most

.

mg/day

that

spe-

of tryptophan B6 levels. This

on since

oral

xanwere

users

and

xanthurenic

acid

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

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 contraceptive

gest

normal the

relatively

of vitamin

on

given

some

primarily

as well

any

controls.

acid Howof cysta-

metabolites

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

20-

to

plasma

levels

decreased

range

PLP. in

information of

was

reported users in subnormal

plasma

subjects

in

However,

had

Further, during

of oral contraceptive normal with continued

dietary biity

low.

study, they contraceptive

34-year-age

of

PLY

the

first

use but tended usage. Since no

presented,

the

contraceptive-induced

changes

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

to the present 20% of oral

levels months toward

correspondingly

on

urinary hydroxyratios

contraceptive acid

significantly

users value

for

in

although the

different

whole

from

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

deficiency

in

study

in

vitamin

certain

subjects.

In

the

of

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

4

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

g

addition,

200 mg were given

sulfate

and

significant

urinary

4-pyri-

pyridoxal phosphate, and and aspartate aminotrans-

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

L-methionine),

plasma alanine

of deficiency,

No

oral

a

it

demonstrate

of estrogen-containing produce

which

maintained, exception

peak tion.

users.

may

In

of

L-kynurenine

Rose et al. (18) found an increased in vitro PLY stimulation of erythrocyte alanine aminotransferase in about 1 5% of contraceptive users. The brief review of the literature presented above indicates that ample evidence exists to suggest

erythrocyte

ferases.

these

induction

B6 deficiency, significant

subjects

B6

study

AL.

3.0 g load doxic acid,

thereof,

of

present

as expected

a vitamin

consistent

aminotrans-

activation

indices

In

changed

control

PLY

reliable

nutrition indices

erythrocyte the

El

load (after

Downloaded from https://academic.oup.com/ajcn/article-abstract/28/5/535/4732916 by Washington University in St. Louis user on 09 April 2018

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 metabolism in women using steroid hormones for ovulation control. Am. J. Chin. Nutr. 20: 452, 1967. 3. LUHBY, A. L., M. BRIN, M. GORDON, P. DAVIS, M. MURPHY AND H. SPIEGEL. Vitamin B6 metabolism in users of oral contraceptive agents. I. Abnormal urinary xanthurenic acid excretion and its correction by pyridoxine. Am. J. Chin. Nutr. 24: 684, 1971. 4. PRICE, S. A., D. P. ROSE AND P. A. lOSELAND. Effects of dietary vitamin B, deficiency and oral contraceptives on the spontaneous urinary excretion of 3-hydroxyanthraniic acid. Am. J. Chin. Nutr. 25: 494, 1972. 5. BROWN, R. R., D. P. ROSE, J. E. LEKLEM, H. LINKSWILER AND R. ANAND. Urinary 4-pyridoxic acid, plasma pyridoxal phosphate, and

VITAMIN

6.

7.

8.

9.

10.

11.

12.

B6

REQUIREMENTS

IN

erythrocyte aminotransferase levels in oral contraceptive users receiving controlled intakes of vitamin B6 . Am. J. Chin. Nutr. 28: 10, 1975. SWAN, P., J. WENTWORTH AND H. LINKSWILER. Vitamin B6 depletion in man: Urinary taurine and sulfate excretion and nitrogen balance. J. Nutr. 84: 220, 1964. PRICE, J. M., R. R. BROWN AND N. YESS. Testing the functional capacity of the tryptophanniacin pathway in man by analysis of urinary metabohites. In: Advances in Metabolic Disorders, edited by R. Levine and R. Luft. New York: Academic, 1965, vol. 2, p. 159. LEKLEM, J. E., R. R. BROWN, D. P. ROSE, H. LINKSWILER AND R. A. AREND. Metabolism of tryptophan and niacin in oral contraceptive users receiving controlled intakes of vitamin B6. Am. J. Chin. Nutr. 28: 146, 1975. THOMSON, A. R., AND B. J. MILES. Ion-exchange chromatography of amino acids: Improvements in the single column system. Nature 203: 483, 1964. PARK, Y. K., AND H. LINKSWILER. Effect of vitamin B6 depletion in adult man on the excretion of cystathionine and other methionine metabolites. J. Nutr. 100: 110, 1970. BRAIDMAN, I. P., AND D. P. ROSE. Effects of sex hormones on three glucocorticoid-inducible enzymes concerned with amino acid metabolism in rat liver. Endocrinology 89: 1250, 1971. MASON, M., AND B. MANNING. Effects of steroid conjugates on availability of pyridoxal phosphate for kynureninase and kynurenine aminotransferase activity. Am. J. Chin. Nutr. 24:

Downloaded from https://academic.oup.com/ajcn/article-abstract/28/5/535/4732916 by Washington University in St. Louis user on 09 April 2018

ORAL

13.

14.

15.

16.

17.

18.

19.

CONTRACEPTIVE

USERS

541

786, 1971. ROSE, D. P., AND R. R. BROWN. The influence of sex and estrogens on liver kynureninase and kynurenine aminotransferase in the rat. Biochim. Biophys. Acta 184: 412, 1969. LUMENG, L., R. E. CLEARY AND 1.-K. LI. Effect of oral contraceptives on the plasma concentration of pyridoxal phosphate. Am. J. Cliri. Nutr. 27: 326, 1974. SALKELD, R. M., K. KNORR AND W. F. KORNER. Ihe effect of oral contraceptives on vitamin B6 status. Chin. Chim. Acta 49: 195, 1973. ROSE, D. P., R. STRONG, P. W. ADAMS AND P. E. HARDING. Experimental vitamin B6 deficiency and the effect of oestrogen-containing oral contraceptives on tryptophan metabolism and vitamin B6 requirements. Chin. Sci. 42: 465, 1972. SAUBERLICH, H. E., J. E. CANHAM, E. M. BAKER, N. RAICA, JR. AND Y. F. HERMAN. Biochemical assessment of the nutritional status of vitamin B6 in the human. Am. J. Chin. Nutr. 25: 629, 1972. ROSE, D. P., R. STRONG, J. FOLKARD AND P. W. ADAMS. Erythrocyte aminotransferase activities in women using oral contraceptives and the effect of vitamin B6 supplementation. Am. J. Chin. Nutr. 26: 48, 1973. ROSE, D. P., AND P. W. ADAMS. Oral contraceptives and tryptophan metabolism: Effects of oestrogen in low dose combined with a progestagen (megestrol acetate) given alone. J. Chin. Pathol. 25: 252, 1972.

Vitamin B6 requirements of women using oral contraceptives.

Fifteen women who used combined estrogen-progestogen oral contraceptives and nine control women were given a vitamin B6-deficient diet for 4 weeks and...
980KB Sizes 0 Downloads 0 Views