Introduction to Human Nutrition

166 Introduction to Human Nutrition

basal conditions. However, as discussed below, homo-

cysteine metabolism is more affected by folate status

than by vitamin B 6 status and, like the tryptophan load

test, the methionine load test is probably not reliable

as an index of vitamin B 6 status in fi eld studies.

Non-nutritional uses of vitamin B 6

Several studies have suggested that oral contraceptives

cause vitamin B 6 defi ciency. As a result of this, supple-

ments of vitamin B 6 of 50–100 mg/day, and some-

times higher, have been used to overcome the side-

effects of oral contraceptives. Similar supplements

have also been recommended for the treatment of the

premenstrual syndrome, although there is little evi-

dence of effi cacy from placebo-controlled trials.

All of the studies that suggested that oral contra-

ceptives cause vitamin B 6 defi ciency used the metabo-

lism of tryptophan as a means of assessing vitamin B 6

nutritional status. When other biochemical markers

of status were also assessed, they were not affected by

oral contraceptive use. Furthermore, most of these

studies were performed using the now obsolete high-

dose contraceptive pills.

Oral contraceptives do not cause vitamin B 6 defi -

ciency. The problem is that estrogen metabolites

inhibit kynureninase and reduce the activity of kyn-

urenine hydroxylase. This results in the excretion of

abnormal amounts of tryptophan metabolites, similar

to what is seen in vitamin B 6 defi ciency, but for a dif-

ferent reason.

N

H

C

H

H 2 C NH 3 +

COO–

Tryptophan

Kynurenine

Tryptophan dioxygenase and

formylkynurenine formamidase

O 2

Hydroxykynurenine

O 2

NADPH

Kynurenine hydroxylase

NADP+

Kynurenine

aminotransferase

Kynurenic acid

Xanthurenic acid

Kynurenine

H 2 O aminotransferase

Kynureninase

3-Hydroxyanthranilic acid

Alanine

3-Hydroxyanthranilic acid oxidase

Aminocarboxymuconic semialdehyde

Total oxidation

via acetyl CoA

Quinolinic acid

for NAD synthesis

Figure 8.12 Oxidative pathway of tryptophan: the basis of the tryptophan load test. Tryptophan dioxygenase (EC 1.13.11.11), formylkynurenine

formamidase (EC 3.5.1.9), kynurenine hydroxylase (EC 1.14.13.9), kynureninase (EC 3.7.1.3).