Am J Clin Nutr 2002;76:1422–7. Printed in USA. © 2002 American Society for Clinical Nutrition
Effects of prune consumption on the ratio of 2-hydroxyestrone to
Sidika E Kasim-Karakas, Rogelio U Almario, Laura Gregory, Heather Todd, Rodney Wong, and Bill L Lasley
Background: A higher urinary ratio of the biologically inactive
estrogen metabolite, 2-hydroxyestrone (2OHE1), to the biologi-
cally active metabolite, 16?-hydroxyestrone (16?OHE1), may be
associated with a lower risk of breast cancer. High fiber intake is
also associated with decreased breast cancer risk.
Objective: We investigated the effects of prunes, which are natu-
rally rich in both soluble and insoluble fiber, on the concentrations
of 2OHE1 and 16?OHE1 and on the ratio of 2OHE1 to 16?OHE1.
Design: Nineteen healthy premenopausal women consumed
their habitual diets for 3 menstrual cycles and then consumed
100 g prunes/d for the next 3 cycles. Concentrations of urinary
2OHE1 and 16?OHE1 were determined during the follicular and
Results: Prune supplementation increased total and soluble
fiber intakes by 4 and 2 g/d, respectively (P < 0.001). Mean
(± SEM) luteal 2OHE1 excretion decreased from 3.92 ± 0.79
to 2.20 ± 0.40 nmol/mmol creatinine during the third cycle
(P = 0.017). Luteal 16?OHE1 excretion decreased from 1.38 ± 0.24
to 0.87 ± 0.10 and 0.87 ± 0.15 nmol/mmol creatinine during the
first and third cycles, respectively (P = 0.018 for both values).
Follicular 16?OHE1 excretion decreased significantly only dur-
ing the first cycle (from 0.82 ± 0.12 to 0.45 ± 0.09 nmol/mmol
creatinine; P = 0.005). The 2OHE1-16?OHE1 ratio did not
change significantly after prune supplementation.
Conclusions: Prune supplementation significantly decreased the
excretion of 16?OHE1 during the follicular phase of the first men-
strual cycle and during the luteal phases of both the first and third
menstrual cycles. The 2OHE1-16?OHE1 ratio did not change
significantly. The potential significance of the decrease in
16?OHE1 excretion, without a change in the 2OHE1-16?OHE1
ratio, on the prevention of estrogen-dependent cancers remains to
Am J Clin Nutr 2002;76:1422–7.
Estrogen exposure is a well-recognized risk factor for breast
cancer (1–3). Research suggests that certain estrogen metabo-
lites may also confer a risk of breast cancer (4). Metabolism of
estrogens involves conversion of estradiol to estrone, which is
then hydroxylated through 2 competing pathways to either
16?-hydroxyestrone (16?OHE1) or 2-hydroxyestrone (2OHE1)
and 4-hydroxyestrone (4OHE1), which are catechol estrogens
(5–8). 16?OHE1 retains its biological activity and therefore is
considered a risk factor. Between the 2 catechol estrogens, 2OHE1
is the major metabolite. It is biologically inactive and may even
1From the Department of Internal Medicine, Division of Endocrinology,
Clinical Nutrition, and Vascular Medicine (SEK-K, RUA, and LG), the Institute
of Toxicology and Environmental Health (HT and BLL), and the Department
of Statistics (RW), University of California, Davis.
2Supported by grants (to SEK-K) from The California Prune Board,
Pleasanton, CA, and the ALSAM Foundation, Los Angeles.
3Reprints not available. Address correspondence to SE Kasim-Karakas,
Division of Endocrinology, University of California at Davis, 4150 V Street,
PSSB Suite G400, Sacramento, CA 95817. E-mail: email@example.com.
Received August 6, 2001.
Accepted for publication February 27, 2002.
have antiestrogenic activity. Thus, 2OHE1 does not promote estro-
gen-dependent cancers and may possibly protect against them.
Therefore, a high ratio of the inactive metabolite, 2OHE1, to the
active metabolite, 16?OHE1, is considered a favorable breast can-
cer risk profile (9, 10).
Several modes of intervention were used to try to increase the
ratio of 2OHE1 to 16?OHE1. Among these, exercise (11), bras-
sica vegetables (12), n?3 fish oils (10, 13), flax seed (14), and
indole-3 carbinol (15, 16) successfully increased the 2OHE1-
16?E1 ratio. However, there are conflicting reports about the
effects of soy protein and isoflavonols (17–19).
The effects of dietary fiber on the 2OHE1-16?OHE1 ratio have
not been conclusively established. High fiber intake is associated
with low estrogen concentrations in plasma and urine and high
concentrations in stool (20–30). Furthermore, this effect may be
independent of the fat content of the diet (31). Nevertheless,
dietary supplementation of insoluble fiber (cellulose and wheat
bran) did not change the 2OHE1-16?OHE1 ratio (10, 14).
Fruits and vegetables, which are natural sources of dietary fiber,
contain soluble as well as insoluble fiber. Animal experiments
show that soluble but not insoluble fiber has protective effects
against breast cancer (32, 33). In addition, phenolic compounds
and xenoestrogens in fruits and vegetables increase the 2OHE1-
16?OHE1 ratio by inducing the cytochrome P450 enzyme and
increasing the production of 2OHE1 (15, 16).
In this study we investigated the effects of prune intake on urinary
excretion of total estrogen conjugates, pregnanediol-3-glucuronide
(PdG), 2OHE1, and 16?OHE1 and on the urinary 2OHE1-
16?OHE1 ratio in healthy women with normal ovarian func-
tion. We hypothesized that prune intake may alter the metab-
olism of estrogens because prunes are a rich source of both
soluble and insoluble fiber and cinnamates (34, 35) and
decrease intestinal transit time (34). Because concentrations
of estrogen metabolites may be affected by the menstrual
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