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Effect of Dietary Flaxseed on Serum Levels of Estrogens and Androgens in Postmenopausal Women


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Flaxseed is a rich source of dietary lignans. Experimental studies suggest lignans may exert breast cancer preventive effects through hormonal mechanisms. Our aim was to study the effects of flaxseed on serum sex hormones implicated in the development of breast cancer. Forty-eight postmenopausal women participated in a 12-wk preintervention-postintervention study. Participants consumed 7.5 g/day of ground flaxseed for the first 6 wk and 15.0 grams/day for an additional 6 wk. Nonsignificant declines were noted over the 12 wk (95% confidence intervals) for estradiol (pg/ml), estrone (pg/ml), and testosterone (pg/ml): -4.4 (-12.6 to 3.9), -3.3 (-7.7 to 1.2), -4.7 (-17.8 to 8.5), respectively. Changes tended to be more pronounced in overweight/obese women, particularly for estrone (-6.5, -11.9 to -1.2; P = .02). Our results suggest that dietary flaxseed may modestly lower serum levels of sex steroid hormones, especially in overweight/obese women.
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Nutrition and Cancer, 60(5), 612–618
Copyright © 2008, Taylor & Francis Group, LLC
ISSN: 0163-5581 print / 1532-7914 online
DOI: 10.1080/01635580801971864
Effect of Dietary Flaxseed on Serum Levels of Estrogens and
Androgens in Postmenopausal Women
Susan R. Sturgeon and Joanna L. Heersink
Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences,
University of Massachusetts Amherst, Amherst, Massachusetts, USA
Stella L. Volpe
Division of Biobehavioral and Health Sciences, School of Nursing, University of Pennsylvania,
Philadelphia, Pennsylvania, USA
Elizabeth R. Bertone-Johnson and Elaine Puleo
Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences,
University of Massachusetts Amherst, Amherst, Massachusetts, USA
Frank Z. Stanczyk
Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California,
Los Angeles, California, USA
Sara Sabelawski
Department of Nutrition, School of Public Health and Health Sciences,
University of Massachusetts Amherst, Amherst, Massachusetts, USA
Kristina W¨
Laboratory of Organic Chemistry, Department of Chemistry, University of Helsinki, Helsinki, Finland
Mindy S. Kurzer
Department of Food Science and Nutrition, University of Minnesota, Saint Paul, Minnesota, USA
Carol Bigelow
Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences,
University of Massachusetts Amherst, Amherst, Massachusetts, USA
Flaxseed is a rich source of dietary lignans. Experimental stud-
ies suggest lignans may exert breast cancer preventive effects
through hormonal mechanisms. Our aim was to study the effects of
flaxseed on serum sex hormones implicated in the development of
breast cancer. Forty-eight postmenopausal women participated in
a 12-wk preintervention–postintervention study. Participants con-
sumed 7.5 g/day of ground flaxseed for the first 6 wk and 15.0
grams/day for an additional 6 wk. Nonsignificant declines were
noted over the 12 wk (95% confidence intervals) for estradiol
(pg/ml), estrone (pg/ml), and testosterone (pg/ml): –4.4 (–12.6 to
Submitted 9 July 2007; accepted in final form 13 September 2007.
Address correspondence to Susan R. Sturgeon, Dr PH, Division of
Biostatistics and Epidemiology, School of Public Health and Health
Sciences, University of Massachusetts, 715 North Pleasant Street,
Amherst, MA 01003-9304. E-mail:
3.9), –3.3 (–7.7 to 1.2), –4.7 (–17.8 to 8.5), respectively. Changes
tended to be more pronounced in overweight/obese women, par-
ticularly for estrone (–6.5, –11.9 to –1.2; P=.02). Our results
suggest that dietary flaxseed may modestly lower serum levels of
sex steroid hormones, especially in overweight/obese women.
Endogenous levels of estrogens and androgens are believed
to play a central role in the etiology of breast cancer (1). After
menopause, most estrogen is derived by the aromatase con-
version of plasma androstenedione to estrone in adipose tissue
(2). Some estrone is metabolized to estradiol. Free estradiol, un-
bound to sex hormone-binding globulin (SHBG) is hypothesized
to be the most biologically active fraction in the breast. Es-
trone sulfate is an abundantly circulating estrogen that serves
as a reservoir for the more biologically active estrogens. Epi-
demiologic studies have indicated that elevated serum levels of
total and free estradiol, estrone, estrone sulfate, and lower lev-
els of SHBG after menopause each substantially increase the
risk of breast cancer (1). Recent cohort studies (3,4), although
not all (5,6), also have suggested that elevated serum levels of
testosterone, free testosterone, and androstenedione may inde-
pendently increase breast cancer risk.
Lignans, naturally occurring compounds structurally simi-
lar to sex steroid hormones, are found in low levels in a wide
variety of grains, fruits, and vegetables (7). In humans, plant
lignans are converted by colonic microflora to the mammalian
lignans, enterolactone and enterodiol (8). Because breast can-
cer incidence rates are lower in Asian countries where women
typically consume diets rich in fruits and vegetables, it has
been hypothesized that lignans may have cancer preventative
Lignans have been shown to inhibit cell proliferation and
reduce mammary tumor incidence in rats (9,10). Experimen-
tal studies imply lignans exert breast cancer preventive effects
through hormonal mechanisms. Specifically, lignans may con-
tribute to decreased bioavailable estrogen in circulation through
inhibition of aromatase activity in adipose tissue (11,12) and in-
creased SHBG synthesis in the liver (9,13). Lignins, precursors
to plant lignans, may be effective in binding to testosterone (14).
Through this binding process, testosterone may be more read-
ily excreted in the bile, thereby potentially lowering circulating
There is limited information on the effect of plant lignan in-
take on serum sex hormone levels in humans. Urinary levels of
enterolactone were associated positively with serum levels of
SHBG and inversely associated with serum levels of estradiol
in one cross-sectional study (15). Another cross-sectional study
reported an inverse association between serum testosterone lev-
els and number of servings of foods rich in dietary lignans (i.e.,
dark brown bread) (16).
Dietary flaxseed is, by far, the richest dietary source of
lignans (17). To date, three intervention studies have evalu-
ated the impact of dietary flaxseed consumption on serum lev-
els of sex hormones in postmenopausal women (18–20). One
randomized cross-over study of 28 postmenopausal nuns re-
ported serum levels of estradiol and estrone sulfate decreased
significantly with flaxseed supplementation, although SHBG
and testosterone concentrations were unchanged (18). Two
other small intervention studies, each involving 20 or fewer
women in the flaxseed treatment group, reported no changes
in serum concentrations of estradiol, estrone, estrone sulfate,
or SHBG associated with a flaxseed diet (19–20). By admin-
istering a well-tolerated flaxseed dose and employing a high-
quality assay to measure hormone levels, this dietary flaxseed
preintervention–postintervention study was designed to ad-
dress potentially important methodologic limitations of prior
studies, specifically noncompliance and hormone measurement
Study Population and Experimental Design
The 48 study participants were recruited from the Amherst,
Massachusetts area using newspaper advertisements and posted
advertisements from December 2003 to June 2004. Eligible
participants were defined as women who had undergone natural
menopause (defined by cessation of menses for one or more
years); were English speaking; did not have any bowel disease,
cancer, or diabetes; had not taken antibiotics in the past 6 mo
(because antibiotics may interfere with the microbial conversion
of plant lignans to mammalian lignans); had not taken certain
medications within the past 6 mo (i.e., hormone therapy, oral
corticosteroids, anticoagulants); and were nonsmokers.
The study was explained at an in-person introductory visit,
and written informed consent was obtained. Subjects were asked
to follow certain dietary restrictions for at least 3 wk prior to
a baseline visit and throughout the follow-up period. Specifi-
cally, participants were requested to avoid flaxseed and flaxseed-
containing foods, all soy and soy products; dietary supplements,
herbs, or teas known to have phytoestrogen activity (specifically
isoflavones, natural estrogens, plant estrogens, genistein, dong
quai, ginseng, black cohosh, Vitex, chastree, wild yam, moth-
erwort, lemon balm, licorice, and red clover); and cruciferous
vegetables (specifically broccoli, broccoli sprouts, brocoflower,
brocolini, Brussels sprouts, cauliflower, cabbage, bok choy, Chi-
nese cabbage, kale, Swiss chard, kohlrabi, rutabaga, turnips,
collard greens, mustard greens, turnip greens, and watercress)
because of their potential effects on endogenous hormone lev-
els. Initially, participants were asked to refrain from alcohol
consumption because it is known to alter endogenous hormone
levels (21). However, this requirement made subject recruitment
difficult. The alcohol requirements were therefore relaxed, re-
quiring subjects to maintain their normal alcohol consumption
but consume no more than two alcoholic beverages per day
and no more than 7 alcoholic beverages per week. Study par-
ticipants were asked to maintain their usual diet and exercise
patterns throughout the study.
At the baseline visit, a 20 ml nonfasting blood specimen was
drawn by a nurse phlebotomist (between the hours of 7:00 AM
and 10:00 AM), and study participants submitted a 24-h urine
specimen that had been collected over the previous day. In addi-
tion, study participants completed a 7-day dietary recall (7DDR;
University of Massachusetts Medical School, Worcester), which
queried dietary intake of 118 food categories or individual foods
and 13 beverage items consumed over the previous week (22).
The 7DDR also evaluates recreational and exercise activities,
occupational activities, and household and childcare activities
over the prior 28-day period. The 7DDR has been validated
cross-sectionally against 24-h dietary recalls in three separate
studies in a total of 261 subjects (23). Height and body weight
was also measured at this visit, and a self-administered ques-
tionnaire was used to elicit information on sociodemographic
factors and standard breast cancer risk factors.
At the baseline visit, study participants were instructed to
consume one tablespoon of ground flaxseed (7.5 g) per day until
the scheduled first follow-up visit, approximately 6 wk later. At
the first follow-up visit, study participants were instructed to
consume two tablespoons of ground flaxseed per day (15 g)
until the second follow-up visit, 6 wk after the first follow-up
visit. As with the baseline visit, at each of the follow-up visits, a
20 ml blood specimen was obtained, and participants provided
a 24-h urine specimen that had been collected over the previous
day. In addition, study participants completed a 7DDR and were
Stabilized flaxseed without any additives was purchased from
the Essential Nutrient Research Corporation (ENRECO, New-
ton, WI). All of the flaxseed used in this study originated from a
single production lot and was shipped to the University of Mas-
sachusetts Amherst in two separate shipments. Whole flaxseed
was stored in cold storage and was ground immediately prior to
shipping. A 1-lb bag of ground flaxseed and a tablespoon mea-
sure with instructions for standard measurement procedures was
provided for each subject at the baseline visit, and any unused
flaxseed was returned at the first follow-up visit. Two 1-lb bags
of ground flaxseed were provided for each subject at the first
follow-up visit, and any unused flaxseed was returned at the
second follow-up visit. Study participants were instructed to
sprinkle it on any cold food of their choice, for example, cot-
tage cheese, yogurt, cereal, applesauce, pudding, or salad. They
were instructed not to cook or bake with the flaxseed. Partici-
pants were provided with already ground flaxseed to maximize
adherence, and were instructed to store the flaxseed in the refrig-
erator to prevent spoiling. The flaxseed that was returned at each
follow-up visit was weighed to determine subject compliance.
Laboratory Analyses
Blood specimens were immediately processed and frozen at
80C. Hormone assays were performed at the Reproductive
Endocrine Research Laboratory at the University of Southern
California, Los Angeles, directed by one of the authors (F. Z.
Stanczyk). For each study participant, all three serum samples
were included in the same analysis batch; the order in which
samples were placed into a batch was randomized. Two repli-
cate quality control blood specimens from two postmenopausal
women were also inserted randomly into each of the 4 batches,
for a total of 16 assessments of laboratory assay quality. Labora-
tory technicians were blinded to the identification of all samples
from study and quality control subjects.
Concentrations of testosterone, estrone, and estradiol were
measured by sensitive and specific radioimmunoassays (RIAs)
after organic solvent extraction and Celite column partition chro-
matography as described previously (24,25). The sensitivities
of the testosterone, estrone, and estradiol RIAs are 1.5 ng/dl,
4 pg/ml, and 3 pg/ml, respectively. SHBG was quantified by
a solid-phase, 2-site, chemiluminescent immunoassay using the
Immulite analyzer (Diagnostic Products Corp., Inglewood, CA).
Bioavailable (non-SHBG bound) testosterone and estradiol con-
centrations were calculated using a validated algorithm on the
basis of total testosterone estradiol, and SHBG concentrations,
as well as an assumed albumin concentration (26–28). Based on
the blinded quality control serum replicates inserted from two
postmenopausal women, intra-assay coefficient of variations,
respectively, were 9.4% and 8.2% for testosterone, 11.5% and
12.9% for estrone, 15.5% and 14.3% for estradiol, and 3.9%
and 3.4% for SHBG.
Urine was collected in containers with ascorbic acid, and
after recording the weight, 0.1% sodium azide was added as a
preservative. Urine specimens were immediately processed and
frozen at 20C and shipped on dry ice to the Department of
Nutrition and Food Science (University of Minnesota, St. Paul).
Urinary concentrations of enterodiol, as a marker of flaxseed
compliance, were measured using a modification of standard
gas-chromatography/mass-spectrometry methods (29).
Statistical Analyses
Dietary and physical activity variables were created from
the 7DDR administered at each of the three visits. Physical
activity levels were calculated as total minutes per week and
metabolic equivalent task (MET) hours per day following the
method of Ainsworth and colleagues (30). Macronutrient and
micronutrient intake in grams per day were adjusted for total
energy intake using the residual method (31).
Repeated measures analysis of variance was performed to
assess the significance of changes over time in hormone levels.
Repeated measures analysis of covariance was used to deter-
mine changes in the hormone levels after adjustment for se-
lected dietary factors, weight, and level of physical activity. Di-
etary factors evaluated included total energy intake and energy
adjusted macronutrients and micronutrients (total fat, total sat-
urated fat, total protein, vegetable protein, animal protein total
carbohydrates, alcohol, total fiber, insoluble fiber, and linoleic
acid). The decision to retain potential confounders in the re-
peated measures analysis of covariance was based on initial
assessments of changes over time in each of the preceding co-
variates and utilized the Ftest (P0.05) in a repeated measures
As shown in Table 1, the study population was mainly non-
Hispanic White (95%) and college educated (74%), with a mean
age of 57 ±4.8 yr. Based on an analysis of the weights of
distributed and returned flaxseed, mean daily flaxseed intake
(±SD) was 7.8 ±1.6 g/day and 15.4 ±2.8 g/day during the
first and second follow-up periods, respectively. Mean urinary
enterodiol levels at baseline, 6 wk, and 12 wk were 0.6 mg/day,
2.39 mg/day, and 5.75 mg/day, respectively, showing a rise as
expected when higher doses of flaxseed were ingested. There
were no changes in study subject weight or level of physical
activity over the intervention period (results not shown). Mean
Baseline Characteristics of Study Participantsa
Characteristic Mean (SD) No.b%
Age (yr) 57 (4.8)
MET (h/day) 2.8 (0.5)
Minutes of activity per week 260 (47)
Total energy intake (kcal/day) 1,732 (139.1)
White 46 94.8
Other 1 2.1
High school or some college 13 27.1
College graduate 35 72.9
Body mass index (kg/m2)
<25 25 53.2
25 22 46.8
Menopausal hormone use (yr)
Never 27 56.3
Ever smoked cigarettes
No 31 64.6
Yes 17 35.4
Family history of breast cancer
No 39 81.3
Yes 9 18.8
History of benign breast disease
No 37 77.1
Yes 11 22.9
an=48. Abbreviation is as follows: MET =metabolic task
bMay not add up to 48 (100%) due to missing data.
body weights (kg) were 67.5, 67.5, and 67.2 at the baseline visit,
first follow-up visit, and second follow-up visit, respectively.
There were small declines in serum levels of testosterone,
estrone, and estradiol after 6 and 12 wk of flaxseed ingestion
among all women, although these declines were not statistically
significant (Table 2). Body mass index (BMI) is a recognized
breast cancer risk factor; the elevated risk in overweight women
likely reflects higher circulating estrogens due to increased aro-
matase activity in adipose tissue (32). At baseline, circulating
levels of estradiol across 3 weight groups (<25, 25–30, >30
kg/m2) were 15.1, 11.1, and 15.6 pg/ml, respectively (P=0.86),
whereas comparable estrone levels were 24.6, 25.9, and 58.6
pg/ml (P<0.001), respectively. Because dietary lignans have
been shown to inhibit aromatase activity (11,12), we examined
the effects of flaxseed on serum sex hormone levels separately in
normal weight (BMI <25 kg/m2) and overweight/obese (BMI
25 kg/m2) women. Among overweight/obese women, we ob-
served a pattern of more substantial declines in serum levels of
testosterone, estrone, and estradiol associated with consuming
flaxseed. The decline among overweight/obese women was sta-
tistically significant for testosterone at 6 wk and for estrone at
6 and 12 wk. Among normal weight women, we also observed
small suggestive declines in serum sex hormone levels, but these
were not statistically significant.
A total of 6 study participants had estradiol concentrations
30 pg/ml at any of the 3 study visits. All study subjects
had follicle-stimulating hormone levels in the postmenopausal
range, and none reported use of hormone therapy during the
study period (results not shown). All analyses were rerun ex-
cluding these participants to determine their impact on the study
findings. Results were generally similar to those reported above.
Among overweight/obese women, for example, there continued
to be statistically significant declines in estrone from baseline to
Follow-Up 1, and from baseline to Follow-Up 2 (–5.9 pg/ml and
–3.9 pg/ml, respectively). There were also statistically signifi-
cant declines from baseline to Follow-Up 1 for testosterone (–
15.9 pg/ml) and estradiol (–1.5 pg/ml), but changes in these hor-
mones were modest and not statistically significant from base-
line to Follow-Up 2 (–6.6 pg/ml and –0.6 pg/ml, respectively).
When we further restricted the data set to 6 obese women
(30 kg/m2; results not shown), we observed statistically sig-
nificant declines between baseline and Follow-Up 1 for testos-
terone (–34.2 pg/ml) and estrone (–18.4 pg/ ml). Comparable
values between baseline and Follow-Up 2 were –15.6 pg/ml and
–10.9 pg/ml, respectively, although these were not statistically
Overall, there was little evidence that consuming a higher
dose of flaxseed for 12 wk resulted in a greater decline in serum
sex hormone levels than consumption of flaxseed for 6 wk in
either subgroup. Serum levels of SHBG were essentially un-
changed between the first and second follow-up visits. Although
mean intake of vegetable protein, carbohydrate, and linoleic acid
changed significantly over the intervention periods, the results
in Table 2 were essentially unchanged after adjustment for these
Consuming 7.5 g of flaxseed per day for 6 wk and 15 g of
flaxseed for an additional 6 wk resulted in modest, nonstatisti-
cally significant declines in serum levels of testosterone, estrone,
and estradiol but not SHBG in this group of postmenopausal
women. In the subset of overweight women, the mean reduc-
tion of 6.5 pg/ml for estrone was statistically significant. In
the randomized cross-over trial of 28 postmenopausal women
by Haggans and colleagues (18), 5 and 10 g/day flaxseed diets
for 7 wk reduced serum concentrations of estradiol and estrone
sulfate but not estrone. By contrast, dietary flaxseed at much
higher prescribed doses (25 g/day for 16 weeks, and 40 g/day
for 3 mo, respectively) have not been shown to alter serum levels
of estrogens or SHBG in 2 small intervention studies (19,20).
The difference between our findings and those from prior stud-
ies may reflect noncompliance to high-dose flaxseed regimens,
Serum Sex Hormone Levels at Baseline and Change Associated With Dietary Flaxseed Intervention Among Postmenopausal
Women and by Category of Body Mass Indexa
Change from Baseline to Change from Baseline to
Baseline Level Follow-Up 1 Follow-Up 2b
Mean Mean (95% CI) PValue % Mean (95% CI) PVal u e %
All women (n=48)c
Testosterone (pg/ml) 181 9.9 (23.8 to 4.0) 0.16 5.5 4.7 (17.8 to 8.5) 0.48 2.6
Estrone (pg/ml) 30.02.6 (6.7to1.5) 0.21 8.7 3.3 (7.7to1.2) 0.15 11.0
Estradiol (pg/ml) 14.12.7 (6.6to1.2) 0.17 19.1 4.4 (12.6 to 3.9) 0.29 31.2
SHBG (nmol/l) 49.10.6(2.5to3.7) 0.71 +1.2 .04 (2.7to2.0) 0.98 0.0
Bioavailable estradiol (pg/ml) 8.90.2 (4.1to3.7) 0.92 2.2 2.8 (7.5to2.0) 0.25 31.4
Bioavailable testosterone (pg/ml) 9.10.7 (1.5 to 0.14) 0.10 7.7 0.4 (1.1to0.4) 0.33 4.4
Overweight/obese (n=22)d
Testosterone (pg/ml) 180 14.6 (28.1 to 1.1) 0.03 8.1 7.0 (18.2 to 4.2) 0.20 3.9
Estrone (pg/ml) 36.37.6 (14.2 to 0.9) 0.03 -19.4 6.5 (11.9 to 1.2) 0.02 18.0
Estradiol (pg/ml) 12.53.6 (9.4 to 2.2) 0.21 -20.9 3.4 (9.3to2.4) 0.24 27.2
SHBG (nmol/l) 38.00.1 (2.1to1.9) 0.93 -0.0 1.1 (3.0to0.8) 0.25 2.9
Bioavailable estradiol (pg/ml) 8.71.1(7.0to9.3) 0.77 +12.6 2.2 (5.6to1.3) 0.21 25.3
Bioavailable testosterone (pg/ml) 10.31.0 (1.7 to 0.2) 0.02 -10.9 0.3 (1.1to0.5) 0.38 2.5
Normal Weight (n=25)e
Testosterone (pg/ml) 182 6.7 (31.6 to 18.2) 0.58 3.7 2.1 (25.9 to 21.7) 0.86 1.2
Estrone (pg/ml) 24.61.4(3.8to6.6) 0.58 +5.7 0.5 (7.8to6.8) 0.88 2.0
Estradiol (pg/ml) 15.62.1 (7.9to3.7) 0.47 13.5 5.3 (20.6 to 10.0) 0.48 34.0
SHBG (nmol/l) 59.91.3(4.5to7.2) 0.64 +2.2 1.1 (5.7to7.9) 0.74 +1.8
Bioavailable estradiol (pg/ml) 9.21.4 (4.7to1.8) 0.38 15.2 3.3 (12.0 to 5.4) 0.44 35.9
Bioavailable testosterone (pg/ml) 8.00.5 (2.0to0.9) 0.47 6.3 0.4 (1.7to0.9) 0.56 5.0
aAbbreviations are as follows: SHBG, sex hormone-binding globulin; BMI, body mass index.
bExcludes 1 woman without a follow-up 2 visit.
cIncludes 1 woman with missing height.
dBMI 25kg/m2.
eBMI <25 kg/m2.
hormone measurement variability, or differences in body weight
across studies.
We observed a decline in testosterone after flaxseed con-
sumption, consistent with a report that plant lignins can bind
and promote excretion of testosterone in the bile (14). In con-
trast to our findings, the randomized cross-over study in post-
menopausal women by Haggans and colleagues (18) observed
no change in testosterone levels. However, in one cross-sectional
study of approximately 250 postmenopausal women in Wis-
consin (16), serum testosterone was inversely associated with
number of servings per week of whole grain products from
the dark bread group (r=–.20, P=0.01). This association
was attributed to lignan content because no overall associa-
tion between dietary fiber and testosterone concentration was
One cross-sectional study of approximately 40 women re-
ported a positive association between urinary excretion of en-
terolactone and serum SHBG, an inverse association between
enterolactone and serum testosterone levels, and an inverse as-
sociation between enterolactone and serum estradiol levels (31).
Similarly to the other intervention studies (18–20), we did not
observe an association between SHBG and flaxseed ingestion
in the present study.
Ziegler (34) highlighted the methodological challenges in
interpreting findings from observational studies on the relation-
ship between lignan exposure and risk of breast cancer. Three
case-control studies (35–37) and 6 cohort studies (38–43) have
examined the relationship between enterolactone in serum or
urine, as markers of lignan exposure, and risk of breast cancer.
The three case-control studies reported substantial reductions
in breast cancer risk after menopause associated with urinary
excretion of enterolactone (35–37). Interestingly, our data are
consistent with observational evidence that an inverse associ-
ation between urinary excretion of lignans and risk of breast
cancer may be more pronounced among women with a higher
BMI (35). Among overweight women, Dai and colleagues (37)
found that breast cancer risk decreased steadily with increas-
ing tertiles of urinary lignan levels (relative risk =1.0, 0.72,
and 0.27). By contrast, the comparable relative risks among
overweight women were 1.0, 1.53, and 0.70. It is possible that
changes in metabolism or in dietary intake after a breast cancer
diagnosis may account for the observed associations in case-
control studies. Of the 5 cohort studies, only one observed an
inverse association between enterolactone exposure and risk
of breast cancer (38). As noted by Ziegler (34), however, sin-
gle measures of enterolactone in biological specimens such as
those used in cohort studies, although capturing potentially im-
portant individual variation in colonic metabolism of dietary
lignans, may result in missed associations, as they do not reflect
integrated long-term exposure.
Three other case-control studies (44–46) and two cohort stud-
ies (47,48) have examined the relation between dietary lignan
intake and risk of breast cancer. Women with higher dietary
lignan intake tended to have reduced breast cancer risk in three
studies (44,45,48). Although dietary measures of lignans may be
better at integrating exposure over a long time period, databases
for lignan content of food may not be comprehensive. In addi-
tion, estimates of breast cancer risk vary depending on which
measures of lignan intake is employed: absolute quantity of
plant lignans (matairesinol and secoisolaciresinol) or estimated
bioavailable lignans (enterolactone and enterodiol) using a con-
version factor derived from an in vitro model for colonic fer-
mentation (34). Other more general limitations of research in
this field have also been noted, including that the level and vari-
ation in lignan exposure is low in most populations studied to
date, and many dietary questionnaires do not include foods that
are especially high in lignan content, including dietary flaxseed.
These limitations would tend to bias the association between
lignans and risk of breast cancer toward the null.
This study has several limitations. First, it was relatively
small and thus small changes in serum sex hormones due to
flaxseed are difficult to detect. In addition, the study lacks a
placebo control group. Nevertheless the findings suggest that
consumption of one to two tablespoons of flaxseed per day for 12
wk may favorably influence estrogen and androgen concentra-
tions, particularly in overweight/obese women. It is also impor-
tant to emphasize flaxseed is a whole food that is notably rich in
lignans, the plant-based omega-3 fatty acid (i.e., alpha-linolenic
acid) and fiber, and it cannot be assumed that a single dietary
component is responsible for observed biological effects. In
summary, additional research focused on clarifying the effects of
flaxseed on breast biology is warranted. Such research is impor-
tant because of the promotion of flaxseed as having breast cancer
preventative effects and its increasing widespread availability.
This research was supported by a grant from the United States
Department of Defense Breast Cancer Research Program (Grant
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... Los participantes de los estudios fueron pacientes con cáncer de próstata previo a la prostatectomía (53)(54), mujeres posmenopáusicas con diagnóstico reciente de cáncer de seno (47) y mujeres posmenopáusicas sanas (46). El tratamiento suministrado en los diferentes ensayos incluyó la ingesta de 7,5 a 30,0 g de linaza molida (51)(52)(53)(54), durante tres (54), cinco (52-53) y doce semanas (51). El efecto de la ingesta de linaza molida se comparó en dos estudios con la información de la línea de base (51,53), en otro contra placebo (52) y en otro estudio se compararon varios grupos de tratamiento contra placebo, así: un grupo que consumió suplementos de linaza molida, un grupo con dieta baja en grasa, un grupo una combinación de dieta baja en grasa más linaza molida y otro grupo control que consumió placebo (54). ...
... Los participantes de los estudios fueron pacientes con cáncer de próstata previo a la prostatectomía (53)(54), mujeres posmenopáusicas con diagnóstico reciente de cáncer de seno (47) y mujeres posmenopáusicas sanas (46). El tratamiento suministrado en los diferentes ensayos incluyó la ingesta de 7,5 a 30,0 g de linaza molida (51)(52)(53)(54), durante tres (54), cinco (52-53) y doce semanas (51). El efecto de la ingesta de linaza molida se comparó en dos estudios con la información de la línea de base (51,53), en otro contra placebo (52) y en otro estudio se compararon varios grupos de tratamiento contra placebo, así: un grupo que consumió suplementos de linaza molida, un grupo con dieta baja en grasa, un grupo una combinación de dieta baja en grasa más linaza molida y otro grupo control que consumió placebo (54). ...
... El tratamiento suministrado en los diferentes ensayos incluyó la ingesta de 7,5 a 30,0 g de linaza molida (51)(52)(53)(54), durante tres (54), cinco (52-53) y doce semanas (51). El efecto de la ingesta de linaza molida se comparó en dos estudios con la información de la línea de base (51,53), en otro contra placebo (52) y en otro estudio se compararon varios grupos de tratamiento contra placebo, así: un grupo que consumió suplementos de linaza molida, un grupo con dieta baja en grasa, un grupo una combinación de dieta baja en grasa más linaza molida y otro grupo control que consumió placebo (54). ...
Objetivo: evaluar los efectos del consumo de linaza sobre el perfil lipídico, control del cáncer y como reemplazo hormonal en la menopausia y en la andropausia. Materiales y métodos: se realizó una revisión sistemática de ensayos clínicos aleatorizados que examinaron los efectos del consumo de linaza sobre el peso corporal, la concentración de lípidos sanguíneos, el control del cáncer y los síntomas menopáusicos, usando las bases de datos de PubMed, Lilacs, OPS, OMS y Cochrane, publicados entre el 1 de enero de 2000 y el 30 de junio de 2010. A los artículos que cumplieron con criterios de inclusión se les evaluó su calidad metodológica. Resultados: fueron incluidos 49 artículos. Los estudios reportan que el consumo de linaza genera pequeños cambios en la concentración de los lípidos sanguíneos, mejora la sintomatología en mujeres menopáusicas, promueve la reducción de índices de proliferación tumoral y el aumento de apoptosis en cáncer de mama y próstata. Conclusiones: los resultados aún no son suficientes para recomendar el uso de la linaza para el control de la hipercolesterolemia en pacientes dislipidémicos. La evidencia favorece la linaza como una alternativa en la terapia coadyuvante del tratamiento del cáncer de mama y de próstata, y en la reducción de síntomas durante la menopausia.
... Hutchins et al. (19) reported that consumption of 5 or 10 g/day ground flaxseed for 7 weeks resulted in reduced estradiol levels in postmenopausal women. Moreover, a clinical trial illustrated the favorable effect of flaxseed on sex hormones, only in overweight and obese women (20). Haidari et al. (21) also found that supplementation with 3 g/day of flaxseed for a period of 12 weeks did not result in any significant reduction in serum testosterone or SHBG levels in patients with PCOS. ...
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Inconsistent data suggest that flaxseed supplementation may have a role in sex hormones. We aimed to carry out a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating effects of flaxseed supplementation on sex hormone profile. PubMed, Scopus, Embase, Cochrane Library, Web of Science databases, and Google Scholar were searched up to March 2023. Standardized mean difference (SMD) was pooled using a random-effects model. Sensitivity analysis, heterogeneity, and publication bias were reported using standard methods. The quality of each study was evaluated with the revised Cochrane risk-of-bias tool for randomized trials, known as RoB 2. Finding from ten RCTs revealed that flaxseed supplementation had no significant alteration in follicle-stimulating hormone (FSH) (SMD: −0.11; 95% CI: −0.87, 0.66: p = 0.783), sex hormone-binding globulin (SHBG) (SMD: 0.35; 95% CI: −0.02, 0.72; p = 0.063), total testosterone (TT) levels (SMD: 0.17; 95% CI: −0.07, 0.41; p = 0.165), free androgen index (FAI) (SMD = 0.11, 95% CI: −0.61, 0.83; p = 0.759), and dehydroepiandrosterone sulfate (DHEAS) (SMD: 0.08, 95%CI: −0.55, 0.72, p = 0.794). Flaxseed supplementation had no significant effect on sex hormones in adults. Nevertheless, due to the limited included trials, this topic is still open and needs further studies in future RCTs.
... In obese postmenopausal women, dietary flaxseed slightly reduces the serum levels of steroid sexual hormones linked to the development of breast cancer (Sturgeon et al., 2008). Flaxseeds have both soluble (one-third) and insoluble (twothirds) dietary fiber. ...
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Flaxseed has been consumed by people for a very long time due to its nutritional value and medicinal applications. In India, flaxseed is used for both culinary and medicinal reasons. About 45% of alpha‐linolenic acid (ALA), 28%–30% protein, and 35% fiber are present in flaxseeds. The finest source of omega‐3 fatty acids for those who do not consume seafood is flaxseed. Flaxseeds have lignin, of which primary lignan is secoisolariciresinol diglycoside, with low amounts of isolariciresinol, lariciresinol, pinoresinol, and matairesinol. Flaxseed is probably safe for most grown‐ups. The daily number of bowel movements may increase if flaxseed is included in the diet. Additionally, it may result in side effects such as gas, bloating, stomach pain, and nausea. Higher dosages are probably going to cause more secondary effects. Due to the nutritional profile of flaxseeds, they exhibit various health benefits which include; improving cardiac health, improving brain development, improving skin health, improving gut health, maintaining blood sugar level, reducing the risk of renal diseases, and several types of cancers. The purpose of this study is to provide a general overview of the nutritional profile, health benefits, value‐added products, and toxicity of flaxseeds.
... Although a complete assessment of flax research as a Functional Food is outside the scope of this article and addressed to readers (Bloedon, L.T. and P. O. Szapary, 2004; Fitzpatrick, K., 2007) [7,25] . Dugani et al. [23] Kaitwah et al. [43] Clark et al. (2001) [12] Dupasquier et al. (2007) [24] Rodriguez-Leyva et al. (2010) [74] Harper et al. (2006) [36,37] Caligiuri et al. (2012) [8] Dietary [26] Saggar et al. (2010) [76] Strugeon et al. (2008) [85] Simbalista et al. (2010) [81] Nowak et al. (2007) [58] Dew et al. (2013) [21] Alpha-linolenic acid because both are needed by the body, but the body can't synthesize them, so they need to be supplied in the diet. In the human body the enzymes needed to synthesize these essential fatty acids are deficient (de Lorgeril et al. 2001) [18] . . ...
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Flaxseed with a high medicinal and functional value can easily be used in energy food processing as a functional ingredient. Flaxseed (Linum usitassimum) is a special functional food with an exceptional mix of important polyunsaturated fatty acids, omega 3 alpha linolenic acid, omega 6 linolenic acid (LA), In view of such functional and medicinal qualities of flaxseed, serious efforts have been made to produce a energy rich foods. Nutraceuticals and functional foods have heath-enhancing and therapeutic properties that are believed to enhance human health to prevent and control various forms of life-threatening disorders. The risk of heart disease, obesity, diabetics, colon and intestinal cancer, etc. is increased due to changing life patterns and faulty eating habits. Flaxseeds are a good source of fiber, vitamins, essential amino acids and minerals, and possess good antioxidant properties and some bioactive compounds.
... Excessive androgen secretion in PCOS conditions causes an increase in the number of immature follicles and it is found that flaxseed significantly reduces serum androgen levels. It has been reported in previous research findings by Sturgeon SR et al. and Debra Novak et al. that a decline in testosterone, oestradiol, and estrone levels was observed following dietary flaxseed supplementation, especially in overweight/obese women (Debra et al., 2007, Sturgeon et al., 2008. ...
Young women of reproductive age are more prone to hormonal/endocrine disorders, the most common being Polycystic Ovarian Syndrome (PCOS). Research in different cultural contexts to enhance the physical, emotional, social, and reproductive health of women has been the focus of several scientific studies. High lignan foods reduce the bioavailability of free testosterone through increasing Sex hormone Binding globulin (SHBG) levels. A randomized single-blind placebo-controlled trial was carried out among women of 20 - 25 years from a single on-campus hostel facility in Chennai, India based on the Rotterdam criteria of PCOS diagnosis. The results showed a statistically significant lower serum free testosterone concentrations (1.02 ± 0.428 ng/dl) in the flax group compared to the placebo (1.64 ± 0.504 ng/dl), after the study period. Similarly, it was noted that the lowered levels of Sex hormone Binding Globulin (SHBG) were elevated to 15.22 ± 14.593 nmol/L as compared to only 9.64 ± 5.124 nmol/L in the placebo though not statistically significant, thus creating a promising platform for improving the imbalances in the hormone levels. Also, elevated serum insulin concentration was lowered in the flax group (15.67 ± 6.928 µU/mL) than the control group (19.09 ± 8.526 µU/mL). The FG score significantly reduced in the flax group thus alleviating the clinical manifestation of hirsutism. Lowering of free testosterone, serum insulin, and elevation of serum SHBG levels is attributed to the phytoestrogen (SDG) present in flaxseeds and can be an ideal alternate replacing the conventional drugs for PCOS.
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An attempt has been made in the present investigation formulate a bread by incorporating the fluor of flax and sunflower seeds with an aim to increase the nutritional and organoleptic properties. Generally, breads are being made from wheat flour which has some inadequacies in terms of lesser protein content, mineral composition, vitamins and fiber contents. Interestingly, millets in general have relatively higher protein, minerals and fiber contents which in turn increases the nutritional and digestible properties of food made from them. Therefore, in the present study, bread formulated with incorporation of Banyard millet (Echinochloa frumentacea), flax seed (Linum usitatissimum) and sunflower seed (Helianthus annuus). Attempt has also been made to examine the organoleptic properties of the developed bread and to identify the suitable packaging techniques. The results obtained have been presented and discussed with up-to-date literature pertaining to this work.
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In poly cystic ovary syndrome multiple cysts formation occurs in female ovaries. It is highly prevalent in developing countries like Pakistan and India. Its symptoms include irregular menstrual cycle, abnormal hair growth pattern, acne and mood swings. This disease is also associated with imbalance in androgen levels (which include testosterone and estrogen) and high insulin levels also called hyperinsulinemia. It also contributes in the development of type 2 diabetes, heart disease and cancers. Seed cycling is a modern method used in alternate medicine of treating PCOS by using different seeds in the different stages of menstrual cycle. In this review article we will find out how seed cycling is effective in the treatment of PCOS. Flax, sesame, pumpkin and sunflower seed combinations are being used at different stages of female menstrual cycle. Flaxseeds contain lignans, omega 3 fatty acids and fibre which help in relieving the symptoms of polycystic ovaries. Sesame and sunflower seeds contain high number of fatty acids and lignans which helps in balancing hormonal disturbances in female. Losing weight by having diet rich in fibre improve the level of cholesterol and it is also beneficial decreasing the level of insulin resistance, which if not treated can progressed into type 2 diabetes mellitus and its complications. Herbal medicine in Ayurveda has shown promising effects in relieving pre- menstrual symptoms, hormonal fluctuations and the co-morbidities.
Linum usitatissimum (Linn.), Commonly known as flaxseed or flaxseed, belongs to the family Linaceae. Flaxseed is a crop of blue flowers that produce small, flat seeds of golden yellow to reddish-brown color. It is a native of the Mediterranean and West Asia. Due to its health benefits associated with the high content of linolenic acid (ALA), flaxseed has played a major role in diet and research. The ALA is an essential omega-3-fatty acid, and also due to its presence a major lignan, i.e. secoisolaricyrcinol diglucoside (SDG). There is also a wide range of uses of flaxseed oil in skin health, anticoagulants, anticancer, ulcer treatment, muscle growth, and weight loss. The nutritional composition of flaxseed is about 30% carbohydrate, 18% protein, and 39% fat. Flaxseed contains most carbohydrates in the form of fiber and contains more than 45% omega-3 fatty acids. It also contains dietary fibers, proteins and polyunsaturated fatty acids. All the ingredients possess different health benefits. Although plant resources are the key ingredient in drug discovery, the popularity of flaxseed always fascinate scientists, the number of articles giving information about the chemical components of flaxseed and its potential clinical use is very little. This review provides a systematic summary of the research completed over the past decade and provides an up-to-date summary of the various bioactive and outlines the relationship between the nutritional and pharmacological use of chemical ingredients and its flaxseed.
This chapter provides an overview of nutritional epidemiology for those unfamiliar with the field. The field of nutritional epidemiology developed from an interest in the concept that aspects of diet may influence the occurrence of human disease. Although it is relatively new as a formal area of research, investigators have used basic epidemiologic methods for more than 200 years to identify numerous essential nutrients. The most serious challenge to research in nutritional epidemiology has been the development of practical methods to measure diet. Because epidemiologic studies usually involve at least several hundred and sometimes hundreds of thousands of subjects, dietary assessment methods must be not only reasonably accurate but also relatively inexpensive. Epidemiologic approaches to diet and disease and the interpretation of epidemiologic data are discussed.
The association of alcohol consumption with increased risk for breast cancer has been a consistent finding in a majority of epidemiologic studies during the past 2 decades. Herein, we summarize information on this association from human and animal investigations, with particular reference to epidemiologic data published since 1995. Increased estrogen and androgen levels in women consuming alcohol appear to be important mechanisms underlying the association. Other plausible mechanisms include enhanced mammary gland susceptibility to carcinogenesis, increased mammary carcinogen DNA damage, and greater metastatic potential of breast cancer cells, processes for which the magnitude likely depends on the amount of alcohol consumed. Susceptibility to the breast cancer–enhancing effect of alcohol may also be affected by other dietary factors (such as low folate intake), lifestyle habits (such as use of hormone replacement therapy), or biological characteristics (such as tumor hormone receptor status). Additional progress in understanding alcohol's enhancing effect on breast cancer will depend on a better understanding of the interactions between alcohol and other risk factors and on additional insights into the multiple biological mechanisms involved.
Research on the relation between phytoestrogens and breast cancer risk has been limited in scope. Most epidemiologic studies have involved Asian women and have examined the effects of traditional soy foods (e.g., tofu), soy protein, or urinary excretion of phytoestrogens. The present study extends this research by examining the effects of a spectrum of phytoestrogenic compounds on breast cancer risk in non-Asian US women. African-American, Latina, and White women aged 35-79 years, who were diagnosed with breast cancer between 1995 and 1998, were compared with women selected from the general population via random digit dialing. Interviews were conducted with 1,326 cases and 1,657 controls. Usual intake of specific phytoestrogenic compounds was assessed via a food frequency questionnaire and a newly developed nutrient database. Phytoestrogen intake was not associated with breast cancer risk (odds ratio = 1.0, 95% confidence interval: 0.80, 1.3 for the highest vs. lowest quartile). Results were similar for pre- and postmenopausal women, for women in each ethnic group, and for all seven phytoestrogenic compounds studied. Phytoestrogens appear to have little effect on breast cancer risk at the levels commonly consumed by non-Asian US women: an average intake equivalent to less than one serving of tofu per week.
Based on experimental and epidemiological evidence it is hypothesized that estrogen increases breast cancer risk by increasing mitotic activity in breast epithelial cells. Aromatase is crucial to the biosynthesis of estrogens and may therefore play a role in breast cancer development. Supporting data for an etiological role of aromatase in breast tumor biology are several-fold. First, the association between weight and postmenopausal breast cancer risk may be mediated by aromatase. Secondly, a pilot study found a higher aromatase expression in normal breast adipose tissue from breast cancer cases as opposed to healthy women. Thirdly, experimental data in animals suggest that aromatase activity predisposes mammary tissue to preneoplastic and neoplastic changes. In a multiethnic cohort study conducted in Los Angeles and on Hawaii we investigated (i) whether the plasma estrone to androstenedione (E1/A) ratio in different ethnic groups was associated with ethnic differences in breast cancer incidence, and (ii) whether genetic variation in the CYP19 gene encoding the P450 aromatase protein was associated with breast cancer risk. The age- and weight-adjusted ethnic specific E1/A ratios ◊100 among women without oophorectomy were 7.92 in African-Americans, 8.22 in Japanese, 10.73 in Latinas and 9.29 in non-Latina Whites (P=0.09). The high E1/A ratio in Latina women was not associated with a high breast cancer incidence; in fact Latina women had the lowest breast cancer incidence in the cohort observed so far. We found no consistent association of an intronic (TTTA)n repeat polymorphism with breast cancer risk in different ethnic groups. This polymorphism was not associated with differences in the plasma E1/A ratio in a way that would predict its functional relevance. We describe a newly identified TTC deletion in intron 5 of the CYP19 gene that is associated with the (TTTA)n repeat polymorphism. Neither this polymorphism, nor a polymorphism at codon 264 in exon VII of the CYP19 gene, was associated with breast cancer. We did not identify any genetic variation in exon VIII in 54 African-American subjects. We identified rare genetic variants of unknown functional relevance in the promoter I.4 of the CYP19 gene in 3 out of 24 Latina women. Further investigation into the role of aromatase in breast cancer etiology is important, given that the
Background: The relation between endogenous steroid hormones and risk for breast cancer is uncertain. Measurement of sex hormone levels may identify women at high risk for breast cancer who should consider preventive therapies. Objective: To test the hypothesis that serum concentrations of estradiol and testosterone predict risk for breast cancer. Design: Prospective case-cohort study. Setting: Four clinical centers in the United States. Participants: 97 women with confirmed incident breast cancer and 244 randomly selected controls; all women were white, 65 years of age or older, and were not receiving estrogen. Measurements: Sex-steroid hormone concentrations were assayed by using serum that was collected at baseline and stored at -190 °C. Risk factors for breast cancer were ascertained by questionnaire. Incident cases of breast cancer were confirmed by review of medical records during an average period of 3.2 years. Results: The relative risk for breast cancer in women with the highest concentration of bioavailable estradiol (≥6.83 pmol/L or 1.9 pg/mL) was 3.6 (95% Cl, 1.3 to 10.0) compared with women with the lowest concentration. The risk for breast cancer in women with the highest concentration of free testosterone compared with those with the lowest concentration was 3.3 (Cl, 1.1 to 10.3). The estimated incidence of breast cancer per 1000 person-years was 0.4 (Cl, 0.0 to 1.3) in women with the lowest levels of bioavailable estradiol and free testosterone compared with 6.5 (Cl, 2.7 to 10.3) in women with the highest concentrations of these hormones. Traditional risk factors for breast cancer were similar in case-patients and controls. Adjustments for these risk factors had little effect on the results. Conclusions: Estradiol and testosterone levels may play important roles in the development of breast cancer in older women. A single measurement of bioavailable estradiol and free testosterone may be used to estimate a woman's risk for breast cancer. Women identified as being at high risk for breast cancer as determined by these hormone levels may benefit from antiestrogen treatment for primary prevention.
Background: The relation between endogenous steroid hormones and risk for breast cancer is uncertain. Measure-ment of sex hormone levels may identify women at high risk for breast cancer who should consider preventive ther-apies.
Using multiple 24-hr recalls (24HR) we tested the Seven Day Dietary Recall (7DDR) developed to assess nutrient exposures, especially lipids, in dietary interventions and other clinical trials requiring measurement of effect over moderate time periods. A total of 261 individuals in three studies completed a 7DDR at the end of a 3- to 5-week period during which 3 to 7 24HR were telephone-administered on randomly selected days. One of these studies and data from one additional study (total n = 678) allowed us to test the ability of the 7DDR to predict serum lipid changes in an intervention setting.In correlation and linear regression analyses, high levels of agreement between 7DDR and 24HR were obtained. For total energy: r = 0.67 and b = 0.69, and for total fat intake (g/day): r = 0.67 and b = 0.80. When 7 days of 24HR were available agreement tended to be higher. For total energy: r = 0.69 and b = 0.95, and for total fat (g/day): r = 0.71 and b = 1.04. Data derived from the 7DDR and fit to the Keys and Hegsted equations closely predicted actual changes in total serum cholesterol (within 15% and 10%, respectively). The 7DDR is a relatively easily administered, sensitive method to assess short-term changes in dietary fat consumption in individuals.