B6 requirement
in oral contraceptive
II. Assessment by tryptophan metabolites, vitamin B6, and pyridoxic acid levels in urine1’2 Elizabeth
A. Donald,3
B.Sc.,
M.S.,
Ph.D.
and
Teresa
It
Boss#{233},4B.Sc.,
M.Sc.
ABSTRACT Data were obtained from seven college-age women who used estrogen-containing oral contraceptives and who volunteered to participate in a metabolic study to investigate the requirement for vitamin Be. They consumed a basal diet containing 0.36 mg/day of the vitamin for 42 days. During the first 10 days (predepletion period) the diet was supplemented with pyridoxine hydrochloride to bring the total intake to 2.06 mg/day. After 32 days of depletion the diet was supplemented with pyridoxine hydrochloride for a daily intake of 0.96, 1.56, and 5.06 mg for 8, 9, and 7 days, respectively. Complete 24-hr urine collections were made and composited. Urine was analyzed for total vitamin B, and 4-pyridoxic acid; and for kynurenine, 3-hydroxykynurenine, kynurenic and xanthurenic acid levels both, before and after 2 g loading doses of L-tryptophan. Results were compared with data obtained from non-oral contraceptive users who consumed a similar diet. Tryptophan metabolites significantly increased during the depletion phase and rapidly decreased with pyridoxine hydrochloride supplementation. A vitamin B, intake of 1.56 mg/day was sufficient to restore all metabolites to original levels in oral contraceptive users. Urinary vitamin B. and 4-pyridoxic acid levels decreased during depletion and were returned to original levels with 1.56 mg/day. An intake of 5.06 mg caused large amounts of each to be lost in the urine. The data obtained suggest that 0.96 mg was not adequate to meet the needs of oral contraceptive users as predepletion levels of most parameters studied had not yet been reached. An intake of 1.56 mg restored levels in almost all subjects and 5.06 mg caused large amounts of vitamin B. and 4.. pyridoxic acid to be excreted. An intake of 1.5 mg is similar to the previously suggested intake for nonusers. Am. J. Clin. Nuir. 32: l04.-1032, 1979.
Women containing gen
levels
using oral contraceptives synthetic estrogen and
combinations
excrete
abnormally
high
after a load dose of tryptophan. Several studies (1-8) have indicated that such abnormalities are correctable by intakes of 20 to 40 mg of pyridoxine hydrochloride (PN-HC1). Other investigators have found that other parameters used to measure the vitamin B6 requirement do not indicate the need for excessive intakes of vitamin B6 by OC users. Lumeng et al. (9) found low plasma pyridoxal levels in only four of 11 subjects who demonstrated abnormally high xanthurenic acid (XA) levels in the urine. Two recent studies (10, 11) assessed vitamin B6 needs in OC users using a multiparameter approach. Findings indicated that 0.8 mg of pyridoxine was not adequate to 1024
of tryptophan
(OC) progesto-
metabolites
The American
Journal
of Clinical
tryptophan metabolism in OC users restored all but XA excretion to initial levels. Vitamin B6 intakes between 0.8 and 2.0 mg also restored urinary 4-pyridoxic correct
but
2.0 mg
acid (4-PA) as well as several parameters in the blood. The authors concluded that OC users had no need for high intakes of vitamin B6, and the use of OC would have limited clinical effect on vitamin B6 nutnture. In the present study a multiparameter approach was also used to assess the requirement for vitamin B6 by OC users. The effect of load-doses of tryptophan on the excretion of
of
metabolites
was
observed;
as well
as the
‘From the Faculty of Home Economics, University Alberta, Edmonton, Alberta, Canada T6G 2M8. 2 Supported in part by a grant from The Medical
Research Council, Ottawa, Professor. 4Sessional Nutrition
32: MAY
1979,
pp.
Canada. Lecturer.
1024-1032.
Printed
in U.S.A.
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/5/1024/4666329 by D Hill Library - Acquis S user on 17 September 2018
The vitamin users
VITAMIN
B6 and
amount of vitamin urine. Requirement level and aspartate
activity
4-PA
in
by pyridoxal amino trans-
in erythrocytes (12).
elsewhere
excreted
as assessed and alanine
has
been
re-
Subjects Eight
eight
college-age
nonusers
women
served
OC
using
and and
as experimental
Subjects
used
a variety
preparation.
of contraceptives
Seven of the and one used
See a previous
eight used a sequential
report
for
one
a
for details
Diet
The diet was similar to one used in a previous study of the vitamin B6 needs in non-OC users (13). The basal diet was supplemented where needed to meet the 1968 Recommended Dietary Allowances (14). The diet contained 0.36 mg of vitamin B6. Energy needs of subjects were libitum, high energy
candy, viously
etc. Details (12).
the
experimental
subjects were given a load dose of on day 2 and day 10. Analyses same tryptophan metabolites were
made on these values on days chromatographic
met foods
have
by supplying, ad such as butter,
been
reported
pre-
days
was
days, as well as for preload 1 and 9. An elution columnmethod, followed by fluor-
to the
analyzed
Atkin’s
design
During the 10-day predepletion phase both control and experimental subjects consumed the basal diet supplemented with 1.7 mg of PN-HC1. The total daily intake was 2.06 mg which met the adult Recommended Dietary Allowances (14) for vitamin B6. Only experimental subjects underwent the depletion They
consumed
the
basal
diet
for
32
days. The diet was then supplemented with PN-HC1 for total daily intakes of vitamin B6 of 0.96, 1.56, and 5.06 mg for 8,9, and 7 days, respectively. studies
Complete 24-hr urine collections were made throughout the study. Collections were composited and frozen at -20C until analyzed. Completeness of collection was checked by determining creatinine levels (15).
for vitamin
method
on
the
post
as described
tryptophan
lyzed for 4-PA byFujitaetal.(l8).
using
load
the
of load
B6 according
ick et al. (17) using Saccharomyces gensis as the test organism. Urine days
method
by Storycarlsber-
collected was
ana-
described
Results Tryptophan
Experimental
Metabolic
in
metric or spectrophometric determinations individual metabolites was used (16). Urine collected on the pretryptophan
(12).
phase.
subject
group have been omitted from calculations of metabolites in urine because oflow creatinine values. A load-dose of 2.0 g of L-tryptOphan was mixed with chocolate and given with breakfast on days 2, 11, 18, 25, 32, 39, 43, 50, 59, and 66 to the experimental subjects. Urine collected on these days (postload) was ana-
Control tryptophan for the
contraceptives
for 1 to 25 months. combination type
Data
1025
lyzed for XA and kynurenic acids (1(A), kynurenine (Kyn), and 3-hydroxykynurenine (3OH-Kyn). Urine collected on days previous to the ones listed above (preload) were analyzed for the same tryptophan metabolites.
control subjects, respectively. Subjects were judged to be healthy and informed consent was obtained from each. Details of subjects have been previously reported (12). Oral
IN OC USERS
metabolites
The amount of Kyn (32.3 ,LM/24 hr) excreted during the 10th day of the predepletion phase by subjects using OC was significantly higher (P < 0.001) than amounts excreted during day 9 (1.2 tM/24 hr) by subjects not using OC when both groups had been given a 2.0 g load-dose of tryptophan (Table 1, Fig. 1). The levels excreted by control subjects given the load-dose were similar to levels found in experimental subjects not given tryptophan. The level of Kyn in the urine collected from subjects using OC significantly increased (P < 0.00 1), both pre- and postload, during
postload
the
depletion
levels
were
phase.
significantly
These
pre-
different
and
(P
a2
60 B6 users 2.06 non
-
users
0.34
0.94 1.54
FIG.
4. Mean
±
SE,4-PAexcretion
in urine. SubjectsusingOC,
-
.:
subjects
the higher levels occurring later in each repletion phase. In the present study, 34, 32, and 29% was excreted for each of the three depletion phases compared with 23% before
of estrogen-containing vitamin B6 deficiency
depletion Based
quirements
began. on the various
parameters
measured,
an intake of 1.5 mg of vitamin B6 was sufficient to meet the needs of most of the OC users, and an intake of 5.0 mg caused large amounts of vitamin B6 and 4-PA to be excreted in the urine. These levels of intake were similar to the suggested intake of 1.5 mg/day for non-OC users (13). In 1975, Leklem et al. (11) reviewed the work reported regarding the vitamin B6 requirements of women using OC. They concluded that evidence did “suggest that the use
not
using
OC may in certain
However, controlled dietary shown clear-cut differences
by OC
OC.
users
...
...
produce subjects”.
research
in vitamin and nonusers
a
had not B6 re-
when
a variety of parameters were used to assess need. The authors suggested that the limited number of subjects studied may have prevented small differences from being statistically significant. The results of the present study (12) support the conclusions of Lekiem et al. (11) that the majority of OC users do not have a higher requirement for vitamin B6 than nonusers. The Barbara
authors acknowledge Lowell-Davis, Carol
the technical Williamson,
assistance and Lois
of La-
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/5/1024/4666329 by D Hill Library - Acquis S user on 17 September 2018
-C
1032
DONALD
belle. The cooperation of the subjects is greatly appreciated, for without them, this study could not have been done.
I.
ROSE, D. P. Excretion of xanthurenic acid in the urine of women taking progestogen-oestrogen preparations. Nature 210: 196, 1966. 2. Rosr., D. P. The influence of oestrogens on tryptophan metabolism in man. Clin. Sci. 31: 265, 1966. 3. PRICE, J. M., M. J. THORNTON AND L. M. MUELLER. Tryptophan metabolism in women using steroid hormones for ovulation control. Am. J. Clin. Nutr. 20:
452, 1967.
4.
R. R., D. P. ROSE, J. M. PRICE AND H. Tryptophan metabolsim as affected by anovulatory agents. Ann. N.Y. Acad. Sci. 166: 44, 1969. ALY, H. E., E. A. DONALD AND M. H. W. SIMPsON. Oral contraceptives and vitamin B6 metabolism. Am. J. Clin. Nutr. 24: 297, 1971. ROSE, D. P., R. STRONG, P. W. Ar4u.is AND P. E. HARDING. Experimental vitamin B, deficiency and the effect ofoestrogen-containing oral contraceptives on tryptophan metabolism and vitamin B, requirements. Cliii. Sci. 42: 465, 1972. LUHBY, A. L., M. BRIN, M. GORDON, P. DAVIS, M. MURPHY AND H. SPIEGEL. Vitamin B, 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. ROSE, D. P., AND P. W. ADAMS. Oral contraceptives and tryptophan metabolism: effects of oestrogen in low dose combined with a progestogen and of a lowdose progestogen (megestrol acetate) given alone. J. Chin. Pathol. 25: 252, 1972. LUMENG, L., R. E. CLEARY AND T. K. LI. Effect of oral contraceptives on the plasma concentration pf pyridoxal phosphate. Am. J. Cliii. Nutr. 27: 326, 1974. BROWN, R. R., D. P. ROSE, J. E. LEKLEM, H. LINKSWILER AND R. ANAND. Urinary 4-pyridoxic acid, plasma pyridoxal phosphate, and erythrocyte amino transferase levels in oral contraceptive users receiving controlled intake of vitamin B,. Am. J. Chin. Nutr. 28: 10, 1975. 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 B,. Am. J. Clin. Nutr. 28: 146, 1975. BossE, T. R., AND E. A. DONALD. The vitamin B, requirement in oral contraceptive users. I. Assessment by pyridoxal level and transferase activity in erythrocytes. Am. J. Chin. Nutr. 32: 1015, 1979. DONALD, E. A., L. D. MCBEAN, M. H. W. SIMPsoN, M. F. SUN AND H. E. ALY. Vitamin B, requirement BROWN,
WOLF.
5.
6.
7.
8.
9.
10.
11.
12.
13.
BOSSE of young 1971.
adult
women.
Am. J. Clin.
Nutr.
24: 1028,
14.
NATIONAL RESEARCH COUNCIL. Recommended Dietary Allowances. (rev. ed. 7). Washington, D.C.: National Academy ofSciences, 1968, publ. no. 1694. 15. OSER, B. L. Hawk’s Physiological Chemistry (14th ed). New York: McGraw Hill Co. 1965. 16. PRICE, J. M., R. R. BROWN AND N. YESS. Testing the functional capacity of the tryptophan-niacin pathway in man by analysis of urinary metabohites. In: Advances in Metabolic Disorders, edited by R. Levine and R. Luft. New York: Academic Press, 1965, vol. 2, p. 159. 17. STORVICK, C. A., E. BENSEN, M. EDWARDS AND M. WOODRING. Chemical and microbiological determination of vitamin B,. Meth. Bioch. Anal. 12: 226, 1964. 18. FUJITA, A., D. FUJITA AND K. FRIJINO. Flurometric determination of vitamin B,. III. Fractional determunation of pyridoxal and 4-pyridoxic acid. 3. Vitmthol. 1: 279, 1955. 19. SANDBERG, A. V. AND W. R. SLAUNWHITE, JR. Transcortin: a corticoid binding protein of plasma. II. Levels in various conditions and the effects of estrogens. J. Chin. Invest. 38: 1290, 1959. 20. KELLER, N., I. U. RICHARDSON AND F. E. YATES. Protein binding and the biological activity of corticosteroids: in vivo induction of hepatic and pancreatic alanine aminotransferase by corticosteroids in normal and estrogen-treated rats. Endocrinology 84: 49, 1969. 2 1. BRIGGS, M., AND M. BRIOGS. Plasma hormone concentrations in women using steroid contraceptives. J. Obstet. Gynecol. Brit. Common. 79: 946, 1972. 22. LUCIS, 0. J., AND R. LUCIS. Oral contraceptives and endocrine changes. Bull. World Health Organ. 46: 443, 1972. 23. SANDBERG, A. A., H. E. ROSENTHAL AND W. R.
SLAUNWHITE,
JR.
Certain
metabolic
effects
of
estro-
Gonadal Hormones and Contraceptive Steroids, edited by H. A. Sathanick, D. M. Kipnes, and R. L. Van der Wide. New York: Plenum Press, 1969. 24. LINDHOHM, J., AND N. SCHULTZ-M#{246}LLER. Plasma and urinary cortisol in pregnancy and during estrogen-gestagen treatment. Scand. J. Chin. Lab. Invest. 31: 119, 1973. 25. 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. 26. ALTMAN, K., AND 0. GREENGARD. Correlation of kynuremne excretion with liver tryptophan pyrrolase levels in disease and after hydrocortisone induction. J. Clin. Invest. 45: 1527, 1966. 27. ROSE, D. P., AND F. M. MCGUINTY. The influence of adrenocorticol hormones and vitamins upon tryptophan metabolism in man. Cliii. Sci. 35: 1, 1968. gens.
In:
Metabolic
Effects
of
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/5/1024/4666329 by D Hill Library - Acquis S user on 17 September 2018
References
AND
in oral contraceptive
II. Assessment by tryptophan metabolites, vitamin B6, and pyridoxic acid levels in urine1’2 Elizabeth
A. Donald,3
B.Sc.,
M.S.,
Ph.D.
and
Teresa
It
Boss#{233},4B.Sc.,
M.Sc.
ABSTRACT Data were obtained from seven college-age women who used estrogen-containing oral contraceptives and who volunteered to participate in a metabolic study to investigate the requirement for vitamin Be. They consumed a basal diet containing 0.36 mg/day of the vitamin for 42 days. During the first 10 days (predepletion period) the diet was supplemented with pyridoxine hydrochloride to bring the total intake to 2.06 mg/day. After 32 days of depletion the diet was supplemented with pyridoxine hydrochloride for a daily intake of 0.96, 1.56, and 5.06 mg for 8, 9, and 7 days, respectively. Complete 24-hr urine collections were made and composited. Urine was analyzed for total vitamin B, and 4-pyridoxic acid; and for kynurenine, 3-hydroxykynurenine, kynurenic and xanthurenic acid levels both, before and after 2 g loading doses of L-tryptophan. Results were compared with data obtained from non-oral contraceptive users who consumed a similar diet. Tryptophan metabolites significantly increased during the depletion phase and rapidly decreased with pyridoxine hydrochloride supplementation. A vitamin B, intake of 1.56 mg/day was sufficient to restore all metabolites to original levels in oral contraceptive users. Urinary vitamin B. and 4-pyridoxic acid levels decreased during depletion and were returned to original levels with 1.56 mg/day. An intake of 5.06 mg caused large amounts of each to be lost in the urine. The data obtained suggest that 0.96 mg was not adequate to meet the needs of oral contraceptive users as predepletion levels of most parameters studied had not yet been reached. An intake of 1.56 mg restored levels in almost all subjects and 5.06 mg caused large amounts of vitamin B. and 4.. pyridoxic acid to be excreted. An intake of 1.5 mg is similar to the previously suggested intake for nonusers. Am. J. Clin. Nuir. 32: l04.-1032, 1979.
Women containing gen
levels
using oral contraceptives synthetic estrogen and
combinations
excrete
abnormally
high
after a load dose of tryptophan. Several studies (1-8) have indicated that such abnormalities are correctable by intakes of 20 to 40 mg of pyridoxine hydrochloride (PN-HC1). Other investigators have found that other parameters used to measure the vitamin B6 requirement do not indicate the need for excessive intakes of vitamin B6 by OC users. Lumeng et al. (9) found low plasma pyridoxal levels in only four of 11 subjects who demonstrated abnormally high xanthurenic acid (XA) levels in the urine. Two recent studies (10, 11) assessed vitamin B6 needs in OC users using a multiparameter approach. Findings indicated that 0.8 mg of pyridoxine was not adequate to 1024
of tryptophan
(OC) progesto-
metabolites
The American
Journal
of Clinical
tryptophan metabolism in OC users restored all but XA excretion to initial levels. Vitamin B6 intakes between 0.8 and 2.0 mg also restored urinary 4-pyridoxic correct
but
2.0 mg
acid (4-PA) as well as several parameters in the blood. The authors concluded that OC users had no need for high intakes of vitamin B6, and the use of OC would have limited clinical effect on vitamin B6 nutnture. In the present study a multiparameter approach was also used to assess the requirement for vitamin B6 by OC users. The effect of load-doses of tryptophan on the excretion of
of
metabolites
was
observed;
as well
as the
‘From the Faculty of Home Economics, University Alberta, Edmonton, Alberta, Canada T6G 2M8. 2 Supported in part by a grant from The Medical
Research Council, Ottawa, Professor. 4Sessional Nutrition
32: MAY
1979,
pp.
Canada. Lecturer.
1024-1032.
Printed
in U.S.A.
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/5/1024/4666329 by D Hill Library - Acquis S user on 17 September 2018
The vitamin users
VITAMIN
B6 and
amount of vitamin urine. Requirement level and aspartate
activity
4-PA
in
by pyridoxal amino trans-
in erythrocytes (12).
elsewhere
excreted
as assessed and alanine
has
been
re-
Subjects Eight
eight
college-age
nonusers
women
served
OC
using
and and
as experimental
Subjects
used
a variety
preparation.
of contraceptives
Seven of the and one used
See a previous
eight used a sequential
report
for
one
a
for details
Diet
The diet was similar to one used in a previous study of the vitamin B6 needs in non-OC users (13). The basal diet was supplemented where needed to meet the 1968 Recommended Dietary Allowances (14). The diet contained 0.36 mg of vitamin B6. Energy needs of subjects were libitum, high energy
candy, viously
etc. Details (12).
the
experimental
subjects were given a load dose of on day 2 and day 10. Analyses same tryptophan metabolites were
made on these values on days chromatographic
met foods
have
by supplying, ad such as butter,
been
reported
pre-
days
was
days, as well as for preload 1 and 9. An elution columnmethod, followed by fluor-
to the
analyzed
Atkin’s
design
During the 10-day predepletion phase both control and experimental subjects consumed the basal diet supplemented with 1.7 mg of PN-HC1. The total daily intake was 2.06 mg which met the adult Recommended Dietary Allowances (14) for vitamin B6. Only experimental subjects underwent the depletion They
consumed
the
basal
diet
for
32
days. The diet was then supplemented with PN-HC1 for total daily intakes of vitamin B6 of 0.96, 1.56, and 5.06 mg for 8,9, and 7 days, respectively. studies
Complete 24-hr urine collections were made throughout the study. Collections were composited and frozen at -20C until analyzed. Completeness of collection was checked by determining creatinine levels (15).
for vitamin
method
on
the
post
as described
tryptophan
lyzed for 4-PA byFujitaetal.(l8).
using
load
the
of load
B6 according
ick et al. (17) using Saccharomyces gensis as the test organism. Urine days
method
by Storycarlsber-
collected was
ana-
described
Results Tryptophan
Experimental
Metabolic
in
metric or spectrophometric determinations individual metabolites was used (16). Urine collected on the pretryptophan
(12).
phase.
subject
group have been omitted from calculations of metabolites in urine because oflow creatinine values. A load-dose of 2.0 g of L-tryptOphan was mixed with chocolate and given with breakfast on days 2, 11, 18, 25, 32, 39, 43, 50, 59, and 66 to the experimental subjects. Urine collected on these days (postload) was ana-
Control tryptophan for the
contraceptives
for 1 to 25 months. combination type
Data
1025
lyzed for XA and kynurenic acids (1(A), kynurenine (Kyn), and 3-hydroxykynurenine (3OH-Kyn). Urine collected on days previous to the ones listed above (preload) were analyzed for the same tryptophan metabolites.
control subjects, respectively. Subjects were judged to be healthy and informed consent was obtained from each. Details of subjects have been previously reported (12). Oral
IN OC USERS
metabolites
The amount of Kyn (32.3 ,LM/24 hr) excreted during the 10th day of the predepletion phase by subjects using OC was significantly higher (P < 0.001) than amounts excreted during day 9 (1.2 tM/24 hr) by subjects not using OC when both groups had been given a 2.0 g load-dose of tryptophan (Table 1, Fig. 1). The levels excreted by control subjects given the load-dose were similar to levels found in experimental subjects not given tryptophan. The level of Kyn in the urine collected from subjects using OC significantly increased (P < 0.00 1), both pre- and postload, during
postload
the
depletion
levels
were
phase.
significantly
These
pre-
different
and
(P
a2
60 B6 users 2.06 non
-
users
0.34
0.94 1.54
FIG.
4. Mean
±
SE,4-PAexcretion
in urine. SubjectsusingOC,
-
.:
subjects
the higher levels occurring later in each repletion phase. In the present study, 34, 32, and 29% was excreted for each of the three depletion phases compared with 23% before
of estrogen-containing vitamin B6 deficiency
depletion Based
quirements
began. on the various
parameters
measured,
an intake of 1.5 mg of vitamin B6 was sufficient to meet the needs of most of the OC users, and an intake of 5.0 mg caused large amounts of vitamin B6 and 4-PA to be excreted in the urine. These levels of intake were similar to the suggested intake of 1.5 mg/day for non-OC users (13). In 1975, Leklem et al. (11) reviewed the work reported regarding the vitamin B6 requirements of women using OC. They concluded that evidence did “suggest that the use
not
using
OC may in certain
However, controlled dietary shown clear-cut differences
by OC
OC.
users
...
...
produce subjects”.
research
in vitamin and nonusers
a
had not B6 re-
when
a variety of parameters were used to assess need. The authors suggested that the limited number of subjects studied may have prevented small differences from being statistically significant. The results of the present study (12) support the conclusions of Lekiem et al. (11) that the majority of OC users do not have a higher requirement for vitamin B6 than nonusers. The Barbara
authors acknowledge Lowell-Davis, Carol
the technical Williamson,
assistance and Lois
of La-
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/5/1024/4666329 by D Hill Library - Acquis S user on 17 September 2018
-C
1032
DONALD
belle. The cooperation of the subjects is greatly appreciated, for without them, this study could not have been done.
I.
ROSE, D. P. Excretion of xanthurenic acid in the urine of women taking progestogen-oestrogen preparations. Nature 210: 196, 1966. 2. Rosr., D. P. The influence of oestrogens on tryptophan metabolism in man. Clin. Sci. 31: 265, 1966. 3. PRICE, J. M., M. J. THORNTON AND L. M. MUELLER. Tryptophan metabolism in women using steroid hormones for ovulation control. Am. J. Clin. Nutr. 20:
452, 1967.
4.
R. R., D. P. ROSE, J. M. PRICE AND H. Tryptophan metabolsim as affected by anovulatory agents. Ann. N.Y. Acad. Sci. 166: 44, 1969. ALY, H. E., E. A. DONALD AND M. H. W. SIMPsON. Oral contraceptives and vitamin B6 metabolism. Am. J. Clin. Nutr. 24: 297, 1971. ROSE, D. P., R. STRONG, P. W. Ar4u.is AND P. E. HARDING. Experimental vitamin B, deficiency and the effect ofoestrogen-containing oral contraceptives on tryptophan metabolism and vitamin B, requirements. Cliii. Sci. 42: 465, 1972. LUHBY, A. L., M. BRIN, M. GORDON, P. DAVIS, M. MURPHY AND H. SPIEGEL. Vitamin B, 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. ROSE, D. P., AND P. W. ADAMS. Oral contraceptives and tryptophan metabolism: effects of oestrogen in low dose combined with a progestogen and of a lowdose progestogen (megestrol acetate) given alone. J. Chin. Pathol. 25: 252, 1972. LUMENG, L., R. E. CLEARY AND T. K. LI. Effect of oral contraceptives on the plasma concentration pf pyridoxal phosphate. Am. J. Cliii. Nutr. 27: 326, 1974. BROWN, R. R., D. P. ROSE, J. E. LEKLEM, H. LINKSWILER AND R. ANAND. Urinary 4-pyridoxic acid, plasma pyridoxal phosphate, and erythrocyte amino transferase levels in oral contraceptive users receiving controlled intake of vitamin B,. Am. J. Chin. Nutr. 28: 10, 1975. 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 B,. Am. J. Clin. Nutr. 28: 146, 1975. BossE, T. R., AND E. A. DONALD. The vitamin B, requirement in oral contraceptive users. I. Assessment by pyridoxal level and transferase activity in erythrocytes. Am. J. Chin. Nutr. 32: 1015, 1979. DONALD, E. A., L. D. MCBEAN, M. H. W. SIMPsoN, M. F. SUN AND H. E. ALY. Vitamin B, requirement BROWN,
WOLF.
5.
6.
7.
8.
9.
10.
11.
12.
13.
BOSSE of young 1971.
adult
women.
Am. J. Clin.
Nutr.
24: 1028,
14.
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